Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT03272347
Collaborator
(none)
123
26
4
51.4
4.7
0.1
Study Details
Study Description
Brief Summary
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
123 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Masking in Part 1, including matching placebo. Masking only to dose in Part 2. No masking in Parts 3 and 4.
Primary Purpose:
Treatment
Official Title:
A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination With Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults
Actual Study Start Date
:
Nov 27, 2017
Actual Primary Completion Date
:
Mar 8, 2021
Actual Study Completion Date
:
Mar 9, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Islatravir 0.25 mg Participants will be treated once daily (QD) with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
Drug: Islatravir
Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.
Other Names:
Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks
Other Names:
Drug: Lamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Other Names:
Drug: Placebo to Doravirine, Tenofovir, Lamivudine
Placebo to Doravirine, Tenofovir, Lamivudine is orally administered QD in tablet form for up to 52 weeks
Other Names:
Drug: Doravirine/Islatravir
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
Other Names:
|
| Experimental: Islatravir 0.75 mg Participants will be treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
Drug: Islatravir
Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.
Other Names:
Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks
Other Names:
Drug: Lamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Other Names:
Drug: Placebo to Doravirine, Tenofovir, Lamivudine
Placebo to Doravirine, Tenofovir, Lamivudine is orally administered QD in tablet form for up to 52 weeks
Other Names:
Drug: Doravirine/Islatravir
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
Other Names:
|
| Experimental: Islatravir 2.25 mg Participants will be treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
Drug: Islatravir
Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.
Other Names:
Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks
Other Names:
Drug: Lamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Other Names:
Drug: Placebo to Doravirine, Tenofovir, Lamivudine
Placebo to Doravirine, Tenofovir, Lamivudine is orally administered QD in tablet form for up to 52 weeks
Other Names:
Drug: Doravirine/Islatravir
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
Other Names:
|
| Active Comparator: Doravirine, Tenofovir, Lamivudine Participants will be treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
Drug: Placebo to Islatravir
Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks
Drug: Placebo to Doravirine
Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks
Drug: Placebo to Lamivudine
Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks
Drug: Doravirine, Tenofovir, Lamivudine
Doravirine, Tenofovir, Lamivudine consisting of 100 mg Doravirine + 300 mg Lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.
Other Names:
Drug: Doravirine/Islatravir
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 [Week 24]
Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 [Week 48]
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
- Number of Participants Experiencing Adverse Events (AEs) up to Week 144 [Up to 144 weeks]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
- Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 [Up to 144 weeks]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Secondary Outcome Measures
- Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen [Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)]
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
- Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen [Up to 48 weeks]
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
- Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen [Up to Week 192]
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
- Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 [Baseline and Week 24]
Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
- Change From Baseline in CD4+ T-cell Count at Week 48 [Baseline and Week 48]
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
- Change From Baseline in CD4+ T-cell Count at Week 96 [Baseline and Week 96]
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
- Change From Baseline in CD4+ T-cell Count at Week 144 [Baseline and Week 144]
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
- Change From Baseline in CD4+ T-cell Count at Week 192 [Baseline and Week 192]
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value.
- Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen [Up to 24 weeks]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
- Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen [Up to 24 weeks]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
- Number of Participants Experiencing AEs From Week 96 Through Study Duration [Week 96 up to Week 192]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
- Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration [Week 96 up to Week 192]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
- Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 [Week 144 up to Week 192]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
- Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 [Week 144 up to Week 192]
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Has HIV-1 infection
-
Is naïve to anti-retroviral therapy (ART).
-
Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study
-
Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance
-
All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.
Exclusion Criteria:
-
Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation
-
Has significant hypersensitivity or other contraindication to any of the components of the study drugs
-
Has a history of malignancy ≤5 years prior
-
Female expects to donate eggs at any time during the study
-
Is breastfeeding or expecting to conceive
-
A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of study treatment
-
Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
-
Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
-
Requires any of the following prohibited medications: Carbamazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan, Nafcillin, Pentostatin
-
Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing informed consent to participate in this current trial
-
Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, protease inhibitor, integrase inhibitor
-
Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV co-infection defined as hepatitis B surface antigen [HBsAg]-positive
-
Has a current (active) diagnosis of acute hepatitis due to any cause
-
Has previously been randomized in a study and received islatravir (MK-8591), DOR, Doravirine, Tenofovir, Lamivudine, or 3TC.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pueblo Family Physicians ( Site 0119) | Phoenix | Arizona | United States | 85015 |
| 2 | University California / Davis ( Site 0101) | Sacramento | California | United States | 95817 |
| 3 | Whitman Walker Clinic ( Site 0108) | Washington | District of Columbia | United States | 20005 |
| 4 | Orlando Immunology Center (OIC) ( Site 0105) | Orlando | Florida | United States | 32803 |
| 5 | Northstar Medical Center ( Site 0102) | Chicago | Illinois | United States | 60657 |
| 6 | Kansas City CARE Clinic ( Site 0106) | Kansas City | Missouri | United States | 64111 |
| 7 | Saint Hope Foundation, Inc. ( Site 0116) | Bellaire | Texas | United States | 77401 |
| 8 | North Texas Infectious Diseases Consultants, PA ( Site 0103) | Dallas | Texas | United States | 75246 |
| 9 | Tarrant County Infectious Disease Associates ( Site 0112) | Fort Worth | Texas | United States | 76104 |
| 10 | The Crofoot Research Center, Inc. ( Site 0118) | Houston | Texas | United States | 77098 |
| 11 | Clinica Arauco Salud ( Site 0200) | Santiago | RM | Chile | |
| 12 | Biomedica Research Group ( Site 0202) | Santiago | Chile | ||
| 13 | Hospital Dr. Hernan Henriquez Aravena ( Site 0203) | Temuco | Chile | ||
| 14 | Hopital Avicenne ( Site 2302) | Bobigny | France | ||
| 15 | Hopital Saint-Andre ( Site 2307) | Bordeaux | France | ||
| 16 | CHU Hotel Dieu ( Site 2308) | Nantes | France | ||
| 17 | CHU de Nice Hopital Archet 1 ( Site 2303) | Nice | France | ||
| 18 | Hopital Bichat - Claude Bernard ( Site 2309) | Paris | France | ||
| 19 | Hopital Pitie Salpetriere ( Site 2305) | Paris | France | ||
| 20 | Hopital Saint Louis ( Site 2306) | Paris | France | ||
| 21 | Centre Hospitalier de Tourcoing ( Site 2301) | Tourcoing | France | ||
| 22 | Brighton and Sussex University Hospitals NHS Trust ( Site 2105) | Brighton | East Sussex | United Kingdom | |
| 23 | Chelsea and Westminster Hospital ( Site 2101) | London | United Kingdom | ||
| 24 | Royal London Hospital ( Site 2103) | London | United Kingdom | ||
| 25 | The Royal Free London NHS Foundation Trust ( Site 2102) | London | United Kingdom | ||
| 26 | North Manchester General Hospital ( Site 2104) | Manchester | United Kingdom |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT03272347
Other Study ID Numbers:
- 8591-011
- 2017-000437-32
First Posted:
Sep 5, 2017
Last Update Posted:
Apr 27, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Treatment-naïve participants ≥18 years of age with human immunodeficiency virus type 1 (HIV-1) were enrolled in this study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated once daily (QD) with 0.25 mg islatravir, 100 mg doravirine (DOR), 300 mg lamivudine (3TC), and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no Protocol-defined Virologic Failure (PDVF), between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Period Title: Overall Study | ||||
| STARTED | 31 | 30 | 31 | 31 |
| Treated | 29 | 30 | 31 | 31 |
| COMPLETED | 0 | 1 | 0 | 2 |
| NOT COMPLETED | 31 | 29 | 31 | 29 |
Baseline Characteristics
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Total of all reporting groups |
| Overall Participants | 31 | 30 | 31 | 31 | 123 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
32.3
(13.3)
|
30.0
(9.0)
|
32.4
(11.8)
|
29.4
(8.9)
|
31.0
(10.9)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
1
3.2%
|
3
10%
|
3
9.7%
|
3
9.7%
|
10
8.1%
|
| Male |
30
96.8%
|
27
90%
|
28
90.3%
|
28
90.3%
|
113
91.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
14
45.2%
|
19
63.3%
|
12
38.7%
|
15
48.4%
|
60
48.8%
|
| Not Hispanic or Latino |
16
51.6%
|
11
36.7%
|
18
58.1%
|
15
48.4%
|
60
48.8%
|
| Unknown or Not Reported |
1
3.2%
|
0
0%
|
1
3.2%
|
1
3.2%
|
3
2.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
1
0.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
6
19.4%
|
6
20%
|
8
25.8%
|
5
16.1%
|
25
20.3%
|
| White |
24
77.4%
|
24
80%
|
21
67.7%
|
24
77.4%
|
93
75.6%
|
| More than one race |
0
0%
|
0
0%
|
2
6.5%
|
0
0%
|
2
1.6%
|
| Unknown or Not Reported |
1
3.2%
|
0
0%
|
0
0%
|
1
3.2%
|
2
1.6%
|
| CD4+ T-Cell Count (cells/mm^3) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [cells/mm^3] |
450.8
(170.0)
|
538.5
(165.5)
|
469.6
(203.3)
|
508.5
(206.8)
|
492.1
(188.5)
|
| Participants with <=100,000 copies/mL of HIV-1 RNA (Count of Participants) | |||||
| Count of Participants [Participants] |
24
77.4%
|
23
76.7%
|
23
74.2%
|
24
77.4%
|
94
76.4%
|
| Participants with >100,000 copies/mL of HIV-1 RNA (Count of Participants) | |||||
| Count of Participants [Participants] |
7
22.6%
|
7
23.3%
|
8
25.8%
|
7
22.6%
|
29
23.6%
|
Outcome Measures
| Title | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 |
|---|---|
| Description | Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Number [Percentage of participants] |
93.1
300.3%
|
100.0
333.3%
|
90.3
291.3%
|
90.3
291.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% confidence intervals (CIs) were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 2.9 | |
| Confidence Interval |
(2-Sided) 95% -12.5 to 18.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 9.6 | |
| Confidence Interval |
(2-Sided) 95% -3.8 to 23.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -16.0 to 16.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 |
|---|---|
| Description | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Number [Percentage of participants] |
89.7
289.4%
|
90.0
300%
|
77.4
249.7%
|
83.9
270.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 6.1 | |
| Confidence Interval |
(2-Sided) 95% -12.2 to 24.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 6.2 | |
| Confidence Interval |
(2-Sided) 95% -12.2 to 24.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -6.1 | |
| Confidence Interval |
(2-Sided) 95% -27.1 to 14.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Number of Participants Experiencing Adverse Events (AEs) up to Week 144 |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Time Frame | Up to 144 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Count of Participants [Participants] |
26
83.9%
|
27
90%
|
24
77.4%
|
27
87.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 2.6 | |
| Confidence Interval |
(2-Sided) 95% -15.7 to 20.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 2.9 | |
| Confidence Interval |
(2-Sided) 95% -15.0 to 20.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | -9.7 | |
| Confidence Interval |
(2-Sided) 95% -29.4 to 10.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Time Frame | Up to 144 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Count of Participants [Participants] |
1
3.2%
|
0
0%
|
2
6.5%
|
1
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -13.4 to 14.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | -3.2 | |
| Confidence Interval |
(2-Sided) 95% -16.4 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 3.2 | |
| Confidence Interval |
(2-Sided) 95% -10.8 to 18.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen |
|---|---|
| Description | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Time Frame | Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 27 | 28 |
| Number [Percentage of participants] |
86.2
278.1%
|
90.0
300%
|
88.9
286.8%
|
96.4
311%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -9.7 | |
| Confidence Interval |
(2-Sided) 95% -26.1 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -6.2 | |
| Confidence Interval |
(2-Sided) 95% -21.5 to 9.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -7.5 | |
| Confidence Interval |
(2-Sided) 95% -23.9 to 8.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen |
|---|---|
| Description | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Time Frame | Up to 48 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 27 | 28 |
| Number [Percentage of participants] |
62.1
200.3%
|
56.7
189%
|
59.3
191.3%
|
60.7
195.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 2.2 | |
| Confidence Interval |
(2-Sided) 95% -23.4 to 27.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -3.7 | |
| Confidence Interval |
(2-Sided) 95% -29.6 to 22.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in percent response | |
| Type of Statistical Test | Other | |
| Comments | The 95% CIs were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -1.3 | |
| Confidence Interval |
(2-Sided) 95% -27.7 to 25.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen |
|---|---|
| Description | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. |
| Time Frame | Up to Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 |
|---|---|
| Description | Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Mean (95% Confidence Interval) [cells/mm^3] |
220.5
|
192.8
|
142.9
|
142.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 78.4 | |
| Confidence Interval |
(2-Sided) 95% 18.8 to 138.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 50.7 | |
| Confidence Interval |
(2-Sided) 95% -31.7 to 133.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -63.0 to 64.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Change From Baseline in CD4+ T-cell Count at Week 48 |
|---|---|
| Description | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Mean (95% Confidence Interval) [cells/mm^3] |
182.0
|
183.0
|
100.7
|
181.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -74.1 to 75.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% -70.7 to 73.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -80.8 | |
| Confidence Interval |
(2-Sided) 95% -165.6 to 4.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Change From Baseline in CD4+ T-cell Count at Week 96 |
|---|---|
| Description | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Time Frame | Baseline and Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Mean (95% Confidence Interval) [cells/mm^3] |
243.4
|
161.3
|
136.5
|
268.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -25.5 | |
| Confidence Interval |
(2-Sided) 95% -134.8 to 83.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -107.6 | |
| Confidence Interval |
(2-Sided) 95% -212.1 to -3.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -132.4 | |
| Confidence Interval |
(2-Sided) 95% -242.9 to -21.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Change From Baseline in CD4+ T-cell Count at Week 144 |
|---|---|
| Description | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Time Frame | Baseline and Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 31 | 31 |
| Mean (95% Confidence Interval) [cells/mm^3] |
204.4
|
209.0
|
162.9
|
270.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -65.6 | |
| Confidence Interval |
(2-Sided) 95% -195.3 to 64.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -61.0 | |
| Confidence Interval |
(2-Sided) 95% -188.7 to 66.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Treatment difference in T-cell count | |
| Type of Statistical Test | Other | |
| Comments | The 95% CI for mean difference in CD4 change was based on t-distribution. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment Difference |
| Estimated Value | -107.1 | |
| Confidence Interval |
(2-Sided) 95% -231.2 to 16.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Change From Baseline in CD4+ T-cell Count at Week 192 |
|---|---|
| Description | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value. |
| Time Frame | Baseline and Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 27 | 28 |
| Count of Participants [Participants] |
18
58.1%
|
20
66.7%
|
14
45.2%
|
16
51.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 4.9 | |
| Confidence Interval |
(2-Sided) 95% -20.3 to 29.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 9.5 | |
| Confidence Interval |
(2-Sided) 95% -15.4 to 33.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | -5.3 | |
| Confidence Interval |
(2-Sided) 95% -30.6 to 20.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received. |
| Arm/Group Title | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | Doravirine, Tenofovir, Lamivudine |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. |
| Measure Participants | 29 | 30 | 27 | 28 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
2
6.5%
|
1
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -17.9 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 0.75 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -17.9 to 8.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Islatravir 2.25 mg, Doravirine, Tenofovir, Lamivudine |
|---|---|---|
| Comments | Difference in % Islatravir vs Doravirine, Tenofovir, Lamivudine | |
| Type of Statistical Test | Other | |
| Comments | Based on Miettinen & Nurminen method. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % |
| Estimated Value | 3.8 | |
| Confidence Interval |
(2-Sided) 95% -11.5 to 20.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Islatravir minus Doravirine/Tenofovir/Lamivudine | |
| Title | Number of Participants Experiencing AEs From Week 96 Through Study Duration |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Time Frame | Week 96 up to Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Time Frame | Week 96 up to Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Time Frame | Week 144 up to Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 |
|---|---|
| Description | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Time Frame | Week 144 up to Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | For All-Cause Mortality: from randomization up to 144 weeks. For AEs: from first treatment up to 144 weeks. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The population analyzed for All-Cause Mortality was all randomized participants. The population analyzed for AEs was all randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received. | |||||||
| Arm/Group Title | Islatravir 0.25mg | Islatravir 0.75mg | Islatravir 2.25mg | Doravirine, Tenofivir, Lamivudine | ||||
| Arm/Group Description | Participants were treated QD with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine, tenofovir, lamivudine for a minimum of 24 weeks. For participants with HIV-1 RNA <50 copies/mL and no PDVF, between week 24 through week 52, 3TC and placebo to doravirine, tenofovir, lamivudine was discontinued. After a minimum 48 weeks of treatment, participants were switched to open label dose of 0.75 mg islatravir and DOR 100 mg QD and continued treatment until Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | Participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and doravirine, tenofovir, lamivudine consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments were discontinued and participants received only doravirine, tenofovir, lamivudine QD open label up to Week 144. At Week 144 participants received the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and continued treatment until Week 192. | ||||
All Cause Mortality |
||||||||
| Islatravir 0.25mg | Islatravir 0.75mg | Islatravir 2.25mg | Doravirine, Tenofivir, Lamivudine | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/31 (0%) | 0/30 (0%) | 0/31 (0%) | 1/31 (3.2%) | ||||
Serious Adverse Events |
||||||||
| Islatravir 0.25mg | Islatravir 0.75mg | Islatravir 2.25mg | Doravirine, Tenofivir, Lamivudine | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/29 (6.9%) | 6/30 (20%) | 2/31 (6.5%) | 4/31 (12.9%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphadenopathy | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Cardiac disorders | ||||||||
| Atrial fibrillation | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||
| Long QT syndrome congenital | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| General disorders | ||||||||
| Death | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Infections and infestations | ||||||||
| Appendicitis | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Dysentery | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Epididymitis | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Large intestine infection | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Pneumonia chlamydial | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Pulmonary tuberculosis | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Ankle fracture | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Burkitt's lymphoma | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Nervous system disorders | ||||||||
| Facial paralysis | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Alcohol withdrawal syndrome | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Suicidal ideation | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Suicide attempt | 0/29 (0%) | 0 | 2/30 (6.7%) | 3 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Islatravir 0.25mg | Islatravir 0.75mg | Islatravir 2.25mg | Doravirine, Tenofivir, Lamivudine | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/29 (72.4%) | 26/30 (86.7%) | 23/31 (74.2%) | 22/31 (71%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphadenopathy | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/31 (3.2%) | 3 | 2/31 (6.5%) | 2 |
| Ear and labyrinth disorders | ||||||||
| Vertigo | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Abdominal pain | 1/29 (3.4%) | 2 | 1/30 (3.3%) | 2 | 2/31 (6.5%) | 2 | 3/31 (9.7%) | 3 |
| Abdominal pain upper | 2/29 (6.9%) | 2 | 3/30 (10%) | 3 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 |
| Aphthous ulcer | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 |
| Diarrhoea | 1/29 (3.4%) | 1 | 5/30 (16.7%) | 7 | 3/31 (9.7%) | 3 | 8/31 (25.8%) | 11 |
| Nausea | 1/29 (3.4%) | 1 | 5/30 (16.7%) | 6 | 3/31 (9.7%) | 3 | 3/31 (9.7%) | 5 |
| Proctitis | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Vomiting | 3/29 (10.3%) | 3 | 3/30 (10%) | 3 | 2/31 (6.5%) | 2 | 2/31 (6.5%) | 5 |
| General disorders | ||||||||
| Asthenia | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 2/31 (6.5%) | 3 |
| Fatigue | 1/29 (3.4%) | 1 | 4/30 (13.3%) | 4 | 2/31 (6.5%) | 2 | 3/31 (9.7%) | 3 |
| Influenza like illness | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 3 |
| Pyrexia | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 4 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Immune system disorders | ||||||||
| Seasonal allergy | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 3 |
| Infections and infestations | ||||||||
| Anal chlamydia infection | 2/29 (6.9%) | 2 | 2/30 (6.7%) | 3 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 |
| Bronchitis | 2/29 (6.9%) | 3 | 7/30 (23.3%) | 7 | 1/31 (3.2%) | 1 | 5/31 (16.1%) | 7 |
| COVID-19 | 0/29 (0%) | 0 | 3/30 (10%) | 3 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 |
| Cellulitis | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 1/31 (3.2%) | 2 | 1/31 (3.2%) | 2 |
| Conjunctivitis | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Escherichia urinary tract infection | 2/29 (6.9%) | 2 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Folliculitis | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 2/31 (6.5%) | 2 |
| Fungal skin infection | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Gastroenteritis | 1/29 (3.4%) | 1 | 1/30 (3.3%) | 1 | 1/31 (3.2%) | 1 | 4/31 (12.9%) | 4 |
| Influenza | 3/29 (10.3%) | 3 | 1/30 (3.3%) | 1 | 1/31 (3.2%) | 1 | 3/31 (9.7%) | 4 |
| Lower respiratory tract infection | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Nasopharyngitis | 2/29 (6.9%) | 4 | 9/30 (30%) | 10 | 2/31 (6.5%) | 2 | 7/31 (22.6%) | 14 |
| Oral herpes | 2/29 (6.9%) | 3 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 |
| Oropharyngeal gonococcal infection | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 |
| Otitis media | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 |
| Paronychia | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 |
| Pharyngitis | 1/29 (3.4%) | 1 | 3/30 (10%) | 3 | 0/31 (0%) | 0 | 4/31 (12.9%) | 5 |
| Proctitis chlamydial | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Proctitis gonococcal | 2/29 (6.9%) | 2 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 |
| Sinusitis | 4/29 (13.8%) | 4 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 2 |
| Syphilis | 5/29 (17.2%) | 5 | 8/30 (26.7%) | 8 | 2/31 (6.5%) | 2 | 6/31 (19.4%) | 7 |
| Tonsillitis | 2/29 (6.9%) | 4 | 3/30 (10%) | 8 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Tooth abscess | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 |
| Upper respiratory tract infection | 2/29 (6.9%) | 2 | 3/30 (10%) | 3 | 3/31 (9.7%) | 4 | 3/31 (9.7%) | 5 |
| Urethritis | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Viral pharyngitis | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Procedural pain | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Weight increased | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 |
| Vitamin D deficiency | 1/29 (3.4%) | 1 | 6/30 (20%) | 6 | 4/31 (12.9%) | 4 | 2/31 (6.5%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 4/31 (12.9%) | 4 | 2/31 (6.5%) | 3 |
| Back pain | 2/29 (6.9%) | 2 | 2/30 (6.7%) | 2 | 3/31 (9.7%) | 4 | 4/31 (12.9%) | 4 |
| Musculoskeletal chest pain | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 |
| Neck pain | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 |
| Osteopenia | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 |
| Pain in extremity | 3/29 (10.3%) | 5 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Anogenital warts | 1/29 (3.4%) | 2 | 2/30 (6.7%) | 2 | 2/31 (6.5%) | 2 | 2/31 (6.5%) | 2 |
| Nervous system disorders | ||||||||
| Dizziness | 1/29 (3.4%) | 1 | 1/30 (3.3%) | 1 | 3/31 (9.7%) | 4 | 1/31 (3.2%) | 1 |
| Headache | 5/29 (17.2%) | 5 | 2/30 (6.7%) | 5 | 5/31 (16.1%) | 6 | 4/31 (12.9%) | 5 |
| Sciatica | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 |
| Syncope | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 |
| Psychiatric disorders | ||||||||
| Adjustment disorder with depressed mood | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Anxiety | 3/29 (10.3%) | 3 | 5/30 (16.7%) | 6 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Depression | 1/29 (3.4%) | 1 | 3/30 (10%) | 4 | 1/31 (3.2%) | 1 | 3/31 (9.7%) | 3 |
| Insomnia | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 3/31 (9.7%) | 3 |
| Renal and urinary disorders | ||||||||
| Nephrolithiasis | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 2/31 (6.5%) | 4 |
| Oropharyngeal pain | 3/29 (10.3%) | 3 | 3/30 (10%) | 3 | 1/31 (3.2%) | 3 | 1/31 (3.2%) | 1 |
| Respiratory disorder | 1/29 (3.4%) | 1 | 2/30 (6.7%) | 3 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 |
| Rhinitis allergic | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 |
| Rhinorrhoea | 0/29 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Sinus congestion | 0/29 (0%) | 0 | 2/30 (6.7%) | 3 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Sneezing | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||
| Eczema | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 |
| Penile ulceration | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 |
| Rash | 3/29 (10.3%) | 4 | 2/30 (6.7%) | 3 | 1/31 (3.2%) | 2 | 1/31 (3.2%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT03272347
Other Study ID Numbers:
- 8591-011
- 2017-000437-32
First Posted:
Sep 5, 2017
Last Update Posted:
Apr 27, 2022
Last Verified:
Mar 1, 2022