Common use of Number of Study Participants Clause in Contracts

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male participants in this part of the study. You will be in this study for about 38 days. This does not include the time between screening and dosing, which can be up to 28 days. This study involves:  1 dosing period  12 overnight stays at the Clinical Research Unit (CRU). You will not be able to leave the CRU during that time  1 follow-up phone call about 4 weeks after the last dose of study drug Your eligibility to take part in another study depends on information from this study. You may be eligible to receive a different study drug in another study as soon as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients is not yet known. One group of up to 6 male participants will be in this part of the study. The dose level of study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment Study Days Ritonavir X X X X Study Day -1: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg dose of study drug given with a single 100 mg dose of ritonavir in the morning; single 100 mg dose of ritonavir given about 12 hours after morning dosing Study Day 2: Single 100 mg dose of ritonavir given about 24 hours after morning dosing on Day 1 The study drug and ritonavir will be given orally (by mouth) as tablets. All doses of ritonavir and study drug will be given with about 8 oz. of water and must be swallowed whole. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. This is a research study. The study drugs will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male participants about 84 people taking part in this part of the studystudy if all dosing groups are done. You will be in this study for up to about 38 days30 days (Groups 1 – 5) or 34 days (Groups 6 and 7). This does not include the time between screening and dosing, which can be up to 28 days. This study involves:  • 1 dosing period  12 with a single admission. The admission has 4 overnight stays at the Clinical Research research Unit (CRU)) for dosing groups 1–5, and 9 overnight stays for dosing groups 6 and 7. You will not be able to leave the CRU during that time  • 1 follow-up visit about 4 weeks after study drug dosing for female participants able to have children • 1 follow-up phone call about 4 weeks after the last dose of study drug dosing for male participants and female participants unable to have children Your eligibility to take part in another study depends on information from this studyprevious studies. You may be eligible to receive a different study drug in another study as soon early as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people is not yet known. One group known Up to 7 groups of up to 6 male participants will be in this part of the study. The dose level of study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a dayare planned. Dosing is planned as follows: Group Number Number of Participants DOSING GROUP NUMBER OF PARTICIPANTS STUDY DAY 1 1 14 A 3 14 C 5 14 E Study Treatment Study Days Ritonavir X X X X Study Day -1A: Single 100 mg dose (one 100 mg tablet) of ritonavir given about 12 hours before Day 1 morning dosing with immediate release (IR – study drug and ritonavir released quickly in the body) MST formulation under fasting conditions Study Day 1Treatment B: Single 100 mg dose (one 100 mg tablet) of the WG formulation under fasting conditions Study Treatment C: Single 300 mg dose of study drug given with a single (three 100 mg tablets) of the IR MST formulation under fasting conditions, if done Study Treatment D: Single 300 mg dose of ritonavir in the morning; single (three 100 mg dose tablets) of ritonavir given about 12 hours after morning dosing the WG formulation under fasting conditions, if done Study Day 2Treatment E: Single 100 mg dose of ritonavir given about 24 hours after morning dosing on Day 1 The study drug and ritonavir will be given orally (by mouth) as tablets. All doses of ritonavir and study drug will be given with about 8 oz. of water and must be swallowed whole. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of one 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of tablet) or 300 mg of study drug with dose (three 100 mg of ritonavir in the morningtablets) under fed conditions, after an overnight fast (nothing if done. Formulation to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. This is a research study. The study drugs will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.determined

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male participants about 12 people taking part in this part of the study. You will be in this part of the study for up to about 38 42 days. This does not include the time between screening and dosing, which can be up to 28 days. This part of the study involves:  • 2 dosing periods during 1 dosing period  continuous admission • 12 overnight stays at the Clinical Research Unit (CRU). ) o You will not be able to leave the CRU during that time  • 1 follow-up phone call about 4 weeks after the last dose There will be at least 7 days between each dose of study drug drug. Eligibility to Participate in Another Drug Study Your eligibility to take part in another study depends on information from the previous study and this study. You may be eligible to receive a different study drug in another study as soon early as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people is not yet known. One group of up to 6 male participants will be in is planned for this part of the study. The dose level of Dosing for this study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment Study Days Ritonavir X X X X Study Day -1: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Days 1-3 Day 1: Single 4 Days 5-7 12 300 mg dose of study drug given with 200 mg of itraconazole 200 mg of itraconazole + 300 mg of study drug 200 mg of itraconazole On Day 1 of Period 1 you will receive a single 100 mg oral dose of ritonavir in the morning; 300 mg of study drug, given as a tablet. You will fast overnight (nothing to eat or drink except water) for at least 10 hours before dosing. On Days 1-3 and 5-7 of Period 2 (Days 5-7 and 9-11 overall), you will receive a single 100 mg oral dose of ritonavir 200 mg of itraconazole, given about 12 as a liquid. You will fast for at least 4 hours after morning before dosing Study with itraconazole. On Day 2: Single 100 mg 4 of Period 2 (Day 8 overall), you will receive a single oral dose of ritonavir given about 24 hours 200 mg of itraconazole after morning dosing on Day 1 The an overnight fast of at least 10 hours. You will also receive a single oral dose of 300 mg of study drug and ritonavir immediately after itraconazole dosing. There will be given orally (by mouth) as tablets4 days between study drug dosing in Period 1 and the start of itraconazole dosing in Period 2. All doses will be taken with water. The total fluid volume of ritonavir the doses of itraconazole and study water will be about 8 oz. (1 cup). Study drug will be given with about 8 oz. of water and water. It must be swallowed whole. All doses must be completely swallowed. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have study drug or itraconazole has been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. This is a research study. The study drugs drug and itraconazole will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male 12 participants taking part in this part of the study. You will be in this study for about 38 47 days. This does not include the time between screening and dosing, which can be up to 28 days. This study involves:  1 5 dosing period periods during one continuous admission  12 20 overnight stays at the Clinical Research Unit (CRU). You will not be able to leave the CRU during that time  1 follow-up phone call about 4 weeks after the last dose of study drug Your eligibility to take part in another study depends on information from this studystudy and previous studies. You may be eligible to receive a different study drug in another study as soon as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used is currently authorized to treat COVID patients is not yet known300 mg twice a day for 5 days. One group of up to 6 male participants will be Dosing in this part of the study. The dose level of study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Study Treatment Sequence Number of Participants Study Period Study Treatment Study Days Ritonavir X X X X Study Day -1A: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg dose of study drug given (two 150 mg tablets, commercial formulation) with a 100 mg of ritonavir (single 100 mg dose tablet) Study Treatment B: 300 mg of study drug (two 150 mg tablets, slower dissolution [slowly dissolves] formulation) with 100 mg of ritonavir in the morning; (single 100 mg dose tablet) Study Treatment C: 300 mg of study drug (two 150 tablets, large particle size formulation) with 100 mg of ritonavir given about 12 hours after morning dosing Study Day 2: Single (single 100 mg dose tablet) Study Treatment D: 300 mg of study drug (liquid suspension formulation) with 100 mg of ritonavir given about 24 hours after morning dosing on Day 1 (single 100 mg tablet) Study Treatment E: 300 mg of study drug (liquid suspension formulation) The study drug and ritonavir will be given orally (by mouth) as tablets). All The liquid suspension doses of ritonavir and study drug will be given with about 8 oz. of water and must be swallowed whole. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, that you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. This is a research are compounded in our pharmacy for use in this study. The study drugs will be given Compounded means that the ingredients are added together and mixed to you only during this study and not after make the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent documentfinal dose.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male participants about 12 people taking part in this part of the study. You will be in this study for about 38 35 days. This does not include the time between screening and dosing, which can be up to 28 days. This study involves:  2 dosing periods during 1 dosing period continuous admission  12 9 overnight stays at the Clinical Research Unit (CRU). You will not be able to leave the CRU during that time  1 follow-up phone call about 4 weeks after the last dose There will be at least 5 days between each dose of study drug rosuvastatin. Eligibility to Participate in Another Drug Study Your eligibility to take part in another study depends on information from the previous studies, ongoing studies, and this study. You may be eligible to receive a different study drug in another study as soon early as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer longer, which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people is not yet known. One group of up to 6 male participants will be in are planned for this part of the study. The dose level of Dosing for this study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment Study Days Ritonavir X X X X Study Day -1: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg dose of study drug given with a single 100 mg dose of ritonavir in the morning; single 100 mg dose of ritonavir given about 12 hours after morning dosing Study Day 2: Single 100 mg dose of ritonavir given about 24 hours after morning dosing on Day 1 The study drug and ritonavir Dosing Period Rosuvastatin will be given orally (by mouth) as tabletsa single 10 mg tablet. All doses of ritonavir and study Study drug will be given with about 8 oz. of water and must be swallowed whole. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have been swallowedas two 100 mg tablets. Both you and the study staff will know which of the above study treatment you are receiving. On Day -11 of each period, you will be given receive a single dose of 100 mg of ritonavir in the evening, about 12 hours standard breakfast before morning dosing on Day 1dosing. On Day 1 of the study, you You will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an fast overnight fast (nothing to eat or drink except water) of for at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dosebefore eating breakfast. On Day 2 1 of the studyPeriod 1, you will receive a single dose be served breakfast about 2 hours before dosing with rosuvastatin. Breakfast should be completely eaten within 20 minutes. Dosing will follow about 100 minutes after completing breakfast. On Day 1 of 100 mg Period 2, you will be served breakfast about 30 minutes before dosing with the study drug. Breakfast should be completely eaten within 20 minutes. Dosing with the study drug will follow within 10 minutes of ritonavir completing breakfast. Dosing with rosuvastatin will follow about 24 1 ½ hours after morning dosing on Day 1study drug dosing. Each dose will be taken with about 8 oz (1 cup) of water. All doses must be completely swallowed. We will check your mouth after each dose to make sure the study drug and rosuvastatin have been swallowed. This is a research study. The study drugs drug and rosuvastatin will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male participants in about 18 people joining this part of the study. You will be in this study for about 38 77 days. This does not include the time between screening and dosing, which can be up to 28 days. This part of the study involves:  • 1 dosing outpatient run-in period  12 overnight stays at (4 weeks) with 4 outpatient visits to the Clinical Research Unit (CRU)) • 1 dosing period during 1 continuous admission. 23 overnight stays at CRU. You will not be able to leave the CRU during that time  • 1 follow-up visit to the CRU about 7 days after the last dose • 1 follow-up phone call about 4 weeks after the last dose of study drug Your eligibility to take part in another study depends on information from this study. You may be eligible to receive a different study drug in another study as soon as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people is not yet known. One group The dose of up to 6 male participants study drug in this part of the study will be determined based on information from the previous dosing groups. Dosing is planned as follows: DOSING GROUP NUMBER OF PARTICIPANTS STUDY DAYS -35 to -29 -28 to -22 -21 to -15 -14 to -8 -7 to -1 1 to 14 1 18 0.6 mg Saxenda 1.2 mg Saxenda 1.8 mg Saxenda 2.4 mg Saxenda 3 mg Saxenda 3 mg Saxenda + TBD* mg study drug or placebo *TBD – to be determined. Dosing for this part of the study will be based on data from the earlier dosing groups. It will be randomly assigned, like the flip of a coin, who receives either study drug or placebo You have about a 1 in 3 chance of being on placebo during the study. On study Day -35, you will visit the CRU for your first injection of Saxenda. It will be given to you by a qualified member of the study staff. Saxenda is given in the abdomen, upper thighs, or upper arms. You will be instructed on how to self-administer Saxenda at home during the 4 week run-in period. You will be given sufficient supplies for dosing at home and instructions about food and beverages relative to the timing of your once daily injections. You will also be instructed on how to store the medication. You will be given a dosing diary to record the dosing time of each dose given at home. You will return to the CRU every week during the outpatient run-in period (Study Days -28, -21, and -14). You will bring your completed dosing diary with you at the time of these visits. During these visits, Saxenda will be administered by the CRU staff and you will be given sufficient supplies for dosing at home. On Study Day -7, you will be admitted to the CRU to continue Saxenda dosing before beginning dosing with study drug or placebo on Study Day 1. Saxenda doses while in the CRU will be given by the study staff, including Day -7 when you check in for the study. You will continue to receive a daily injection of Saxenda through Day -1 of the study. On Day -1 you will fast overnight for at least 10 hours before an OGTT. It will be done at about the same time as scheduled for Day 4. From Days 1 to 14, you will continue to receive Saxenda as a daily injection and you will also receive oral doses of study drug or placebo. On Days 1 – 3 and 5 - 14, you will fast overnight for at least 10 hours before receiving a standard breakfast. Breakfast will be provided about 30 minutes before dosing. It should be completely eaten within 20 minutes. Dosing will take place about 10 minutes after completing breakfast. Saxenda dosing will be within 5 minutes of study drug or placebo dosing. On Day 4, you will fast overnight for at least 10 hours before receiving a single oral dose of study drug or placebo. About 30 minutes after dosing, an OGTT will be done. The timing of the OGTT may be changed based on the study drug blood levels from earlier in the study. An OGTT involves drinking an 8 oz solution containing 75 grams of sugar. It measures how well the body can break down sugar. A blood sample is taken before drinking the solution and approximately 4½ hours after. During this time period, blood samples will be collected approximately every 30 minutes. Both you and the study staff will not know whether you are receiving the study drug or placebo. In case of a medical emergency, the study investigator can find out what you have received if considered necessary. The doses of study drug and placebo that you receive may be compounded in our pharmacy for use in this part of the study. The dose level of study drug in this cohort Compounded means that the ingredients are added together and mixed to make the final dose(s). All oral doses will be lower than the highest dose level already evaluated in healthy western participants in Part 1 taken with water. The total fluid volume of doses and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment Study Days Ritonavir X X X X Study Day -1: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg dose of study drug given with a single 100 mg dose of ritonavir in the morning; single 100 mg dose of ritonavir given about 12 hours after morning dosing Study Day 2: Single 100 mg dose of ritonavir given about 24 hours after morning dosing on Day 1 The study drug and ritonavir water will be given orally about 8 oz (by mouth) as tablets1cup). All doses of ritonavir and study drug will be given with about 8 oz. of water and must be swallowed wholecompletely swallowed. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses study drug or placebo have been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. swallowed This is a research study. The study drugs drug and Saxenda will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male about 30 participants taking part in this part of the study. You will be in this study for about 38 45 days. This does not include the time between screening (the period during which your eligibility for participation in this study will be assessed) and dosing, which can be up to 28 days. This study involves:  1 4 dosing period periods during one continuous admission  12 18 overnight stays at the Clinical Research Unit (CRU). You will not be able to leave the CRU during that time  1 follow-up phone call about 4 weeks after the last dose of study drug There will be at least 5 days between each dose. Your eligibility to take part in another study depends on information from this study and the ongoing study. You may be eligible to receive a different study drug in another study as soon as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer longer, which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people with cancer is not yet known. One group of up to 6 male participants will be is planned. Dosing in this part of the study. The dose level of study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment Study Days Ritonavir X X X X Study Day -1A: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg dose of study drug given (two 125 mg and two 25 mg tablets) IR MST faster dissolution (faster dissolving), fasted (without food) Study Treatment B: 300 mg of study drug (two 125 mg and two 25 mg tablets) IR MST moderate dissolution, fasted Study Treatment C: 300 mg of study drug (four 75 mg tablets) IR DC batch moderate dissolution, fasted Study Treatment D: 300 mg of study drug (four 75 mg tablets) IR DC Continuous (slower dissolution), fasted Study Treatment E: 300 mg of study drug (four 75 mg tablets) IR DC Batch moderate dissolution, fed (with food) An IR (immediate release) formulation releases the active ingredients of a single 100 mg dose drug in a short period of ritonavir time. MST (material sparing tablet) means that these tablets were developed on a small scale in order to keep the morning; single 100 mg dose use of ritonavir given about 12 hours after morning dosing Study Day 2: Single 100 mg dose materials low. DC (direct compression) is a manufacturing process. Your study treatment sequence will be randomly assigned, like pulling a number out of ritonavir given about 24 hours after morning dosing on Day 1 a hat. Both you and the study staff will know what you are receiving. The study drug and ritonavir will be given orally (by mouth). On Day 1 of each period, you will receive a single oral dose of study drug. You will fast overnight (nothing to eat or drink except water) as tabletsfor at least 10 hours before dosing or beginning breakfast. All doses of ritonavir and study drug When dosing in the fed state, you will be given served breakfast about 30 minutes before dosing. Breakfast should be completely eaten within 20 minutes. Dosing will follow within 10 minutes of completing breakfast. When dosing in the fasting state, you will not receive breakfast on Day 1 of all fasted periods. An example of a high-fat breakfast includes: 2 eggs fried in butter, 2 strips of pork bacon, 2 slices of toast with about butter, 4 oz. of hash brown potatoes, and 8 oz. of water and whole milk. All of the breakfast items should be eaten in 20 minutes. If you agree to be in this study, you are agreeing to eat all the food listed in this menu. Each dose will be taken with about 8 oz of water. The doses must be swallowed whole. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have study drug has been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. This is a research study. The study drugs will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male participants in about 18 people joining this part of the study. You will be in this study for about 38 77 days. This does not include the time between screening and dosing, which can be up to 28 days. This part of the study involves:  • 1 dosing outpatient run-in period  12 overnight stays at (4 weeks) with 4 outpatient visits to the Clinical Research Unit (CRU)) • 1 dosing period during 1 continuous admission. 25 overnight stays at CRU. You will not be able to leave the CRU during that time  • 1 follow-up visit to the CRU about 7 days after the last dose • 1 follow-up phone call about 4 weeks after the last dose of study drug Your eligibility to take part in another study depends on information from this study. You may be eligible to receive a different study drug in another study as soon as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people is not yet known. One group The dose of up to 6 male participants study drug in this part of the study will be determined based on information from the previous dosing groups. Dosing is planned as follows: DOSING GROUP NUMBER OF PARTICIPANTS STUDY DAYS -35 to -29 -28 to -22 -21 to -15 -14 to -8 -7 to -1 1 to 14 1 18 0.6 mg Saxenda 1.2 mg Saxenda 1.8 mg Saxenda 2.4 mg Saxenda 3 mg Saxenda 3 mg Saxenda + TBD* mg study drug or placebo *TBD – to be determined. Dosing for this part of the study will be based on data from the earlier dosing groups. It will be randomly assigned, like the flip of a coin, who receives either study drug or placebo You have about a 1 in 3 chance of being on placebo during the study. On study Day -35, you will visit the CRU for your first injection of Saxenda. It will be given to you by a qualified member of the study staff. Saxenda is given in the abdomen, upper thighs, or upper arms. You will be instructed on how to self-administer Saxenda at home during the 4 week run-in period. You will be given sufficient supplies for dosing at home and instructions about food and beverages relative to the timing of your once daily injections. You will also be instructed on how to store the medication. You will be given a dosing diary to record the dosing time of each dose given at home. You will return to the CRU every week during the outpatient run-in period (Study Days -28, -21, and -14). You will bring your completed dosing diary with you at the time of these visits. During these visits, Saxenda will be administered by the CRU staff and you will be given sufficient supplies for dosing at home. On Study Day -7, you will be admitted to the CRU to continue Saxenda dosing before beginning dosing with study drug or placebo on Study Day 1. Saxenda doses while in the CRU will be given by the study staff, including Day -7 when you check in for the study. You will continue to receive a daily injection of Saxenda through Day -1 of the study. On Day -1 you will fast overnight for at least 10 hours before an OGTT. It will be done at about the same time as scheduled for Day 8. From Days 1 to 14, you will continue to receive Saxenda as a daily injection and you will also receive oral doses of study drug or placebo. On Days 1 – 7 and 9 - 14, you will fast overnight for at least 10 hours before receiving a standard breakfast. Breakfast will be provided about 30 minutes before dosing. It should be completely eaten within 20 minutes. Dosing will take place about 10 minutes after completing breakfast. Saxenda dosing will be within 5 minutes of study drug or placebo dosing. On Day 8, you will fast overnight for at least 10 hours before receiving a single oral dose of study drug or placebo. About 30 minutes after dosing, an OGTT will be done. The timing of the OGTT may be changed based on the study drug blood levels from earlier in the study. An OGTT involves drinking an 8 oz solution containing 75 grams of sugar. It measures how well the body can break down sugar. A blood sample is taken before drinking the solution and approximately 2½ hours after. During this time period, blood samples will be collected approximately every 30 minutes. Both you and the study staff will not know whether you are receiving the study drug or placebo. In case of a medical emergency, the study investigator can find out what you have received if considered necessary. The doses of study drug and placebo that you receive may be compounded in our pharmacy for use in this part of the study. The dose level of study drug in this cohort Compounded means that the ingredients are added together and mixed to make the final dose(s). All oral doses will be lower than the highest dose level already evaluated in healthy western participants in Part 1 taken with water. The total fluid volume of doses and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment Study Days Ritonavir X X X X Study Day -1: Single 100 mg dose of ritonavir given about 12 hours before Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg dose of study drug given with a single 100 mg dose of ritonavir in the morning; single 100 mg dose of ritonavir given about 12 hours after morning dosing Study Day 2: Single 100 mg dose of ritonavir given about 24 hours after morning dosing on Day 1 The study drug and ritonavir water will be given orally about 8 oz (by mouth) as tablets1cup). All doses of ritonavir and study drug will be given with about 8 oz. of water and must be swallowed wholecompletely swallowed. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses study drug or placebo have been swallowed. Both you and the study staff will know which of the above you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. swallowed This is a research study. The study drugs drug and Saxenda will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.

Number of Study Participants. This study is being done at about 2 different study sites in 2 countries. There will be up to 6 male about 12 participants taking part in this part of the study. You will be in this study for about 38 40 days. This does not include the time between screening and dosing, which can be up to 28 days. This study involves:  • 3 dosing periods during 1 dosing period  12 continuous admission • 14 overnight stays at the Clinical Research Unit (CRU). You will not be able to leave the CRU during that time  • 1 follow-up phone call about 4 weeks after the last dose of study drug There will be at least 5 days between each dose Your eligibility to take part in another study depends on information from this study and the ongoing study. You may be eligible to receive a different study drug in another study as soon as 30 days after your last dose of study drug in this study. This is true for most drugs. Some drugs may stay in your body longer which means that you may have to wait longer before joining another study. These results are usually known after your last blood sample is tested. We will tell you this as soon as possible. We will also tell you if there is a longer than usual period of time that you should not be in another drug study after this one. Our goal is to keep you from doing anything that might potentially harm you. The dose of the study drug that will be used to treat COVID patients people with cancer is not yet known. One group of up to 6 male participants will be Dosing in this part of the study. The dose level of study drug in this cohort will be lower than the highest dose level already evaluated in healthy western participants in Part 1 and Part 2 of the study. Part 1 tested up to 750 mg with ritonavir. Part 2 tested up to 500 mg of study drug with 100 mg ritonavir 2 times a day. Dosing is planned as follows: Group Number Number of Participants Study Treatment A Study Days Ritonavir X X X X Treatment B Study Day -1Treatment C 6 Study Treatment B Study Treatment A Study Treatment C Study Treatment A: Single 200 mg of study drug (two 100 mg tablets) under fasted conditions (without food) Study Treatment B: 200 mg of study drug (two 100 mg tablets) after a low-fat meal Study Treatment C: 200 mg of study drug (two 100 mg tablets) after a high-fat meal The dose of ritonavir given about 12 hours before in Period 3 may be decreased based on the safety data from the first 2 study periods. On Day 1 morning dosing with study drug and ritonavir Study Day 1: Single 300 mg of each period, you will receive a single oral dose of study drug given with a single 100 mg dose of ritonavir drug. You will fast overnight (nothing to eat or drink except water) for at least 10 hours before dosing or beginning breakfast. When dosing in the morning; single 100 mg dose fed state (Periods 1 or 2 and 3), you will be served breakfast about 30 minutes before dosing. Breakfast should be completely eaten within about 20 minutes. Dosing will follow within 10 minutes of ritonavir given about 12 hours after morning completing breakfast. When dosing Study Day in the fasting state (Period 1 or Period 2: Single 100 mg dose of ritonavir given about 24 hours after morning dosing ), you will not receive breakfast on Day 1 The study drug 1. An example of a high-fat breakfast includes: 2 eggs fried in butter, 2 strips of pork bacon, 2 slices of toast with butter, 4 oz. of hash brown potatoes, and ritonavir will be given orally (by mouth) as tablets8 oz of whole milk. All doses An example of ritonavir a low-fat breakfast includes: one boiled egg, one packet of flavored instant oatmeal made with water and study drug will be given with about 8 oz. of water 1 % fat milk. All of each breakfast should be eaten in about 20 minutes. If you agree to be in this study, you are agreeing to eat all the food listed in this menu. You must be able to eat meat and animal products for the high fat and low-fat breakfasts. Each dose will be taken with about 8 oz of water. Doses must be swallowed whole. We will check your mouth after each dose of ritonavir and ritonavir with study drug to make sure the doses have study drug has been swallowed. Both you and the study staff will know which of the above what you are receiving. On Day -1, you will be given a single dose of 100 mg of ritonavir in the evening, about 12 hours before morning dosing on Day 1. On Day 1 of the study, you will be given a single dose of 300 mg of study drug with 100 mg of ritonavir in the morning, after an overnight fast (nothing to eat or drink except water) of at least 10 hours. You will receive a single 100 mg dose of ritonavir about 12 hours after the morning dose. On Day 2 of the study, you will receive a single dose of 100 mg of ritonavir about 24 hours after morning dosing on Day 1. This is a research study. The study drugs drug will be given to you only during this study and not after the study is over. Before any study procedures begin, you will be asked to read, sign, and date this consent document.