Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02217904
Other study ID # 8591-003
Secondary ID 2014-002192-28MK
Status Completed
Phase Phase 1
First received
Last updated
Start date September 17, 2015
Est. completion date May 11, 2017

Study information

Verified date July 2019
Source Merck Sharp & Dohme Corp.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral therapy (ART) activity of islatravir (MK-8591) monotherapy in ART-naive, human immunodeficiency virus-1 (HIV-1) infected participants. The primary hypothesis is that at a safe and tolerable dose of islatravir, the true mean difference in the plasma HIV-1 ribonucleic acid (RNA) reduction from baseline between islatravir and placebo is at least 0.5 log (base10) copies/mL.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date May 11, 2017
Est. primary completion date May 11, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 60 Years
Eligibility Inclusion Criteria:

- Non-pregnant, non-breast feeding, postmenopausal or surgically sterile female

- Female with reproductive potential agrees to use (or have male partner use) two acceptable methods of birth control

- Male agrees to use acceptable method of contraception during study and for 90 days after last dose of trial drug

- Has stable baseline health, other than HIV infection

- Has no significantly abnormal electrocardiogram

- Is HIV-1 positive

- Have a screening plasma HIV-1 RNA = 10,000 copies/mL within 30 days prior to the treatment phase of this study. For inclusion in Panel Islatravir Extended Observation, participants must also have a screening plasma HIV-1 RNA = 25,000 copies/mL within 30 days prior to the treatment phase.

- Is ART naive

- Has not received any investigational agent or marketed ART within 30 days of trial drug administration

- Is diagnosed with HIV-1 infection >= 3 months prior to screening

- Is willing to receive no other ART during treatment phase of study

- Has no evidence of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs)

Exclusion Criteria:

- Is mentally or legally institutionalized/incapacitated, or has significant emotional problems, or has a history of clinically significant psychiatric disorder of the last 5 years

- Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, major neurological abnormalities or diseases

- Has a history of cancer (malignancy)

- Has a history of significant multiple and/or severe allergies, or had an anaphylactic reaction to drugs or food

- Is positive for hepatitis B surface antigen

- Has a history of chronic Hepatitis C

- Had major surgery or lost 500 mL of blood with 4 weeks prior to screening visit

- Has participated in another investigational trial within 4 weeks prior to dosing visit

- Will use any medications, prescribed drugs, or herbal remedies 4 weeks prior to dosing of trial drug, up to the post-trial visit

- Consumes excessive amounts of alcohol, caffeinated beverages, or tobacco products

- Uses illicit drugs or has a history of drug abuse within the prior 2 years

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
1 mg islatravir
Single oral dose of 1 mg islatravir administered following =8 hour fast
2 mg islatravir
Single oral dose of 2 mg islatravir administered following =8 hour fast
10 mg islatravir
Single oral dose of 10 mg islatravir administered following =8 hour fast
30 mg islatravir
Single oral dose of 30 mg islatravir administered following =8 hour fast
0.5 mg islatravir
Single oral dose of 0.5 mg islatravir administered following =8 hour fast
0.25 mg islatravir
Single oral dose of 0.25 mg islatravir administered following =8 hour fast

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches. Baseline and 168 hours (7 days) post-dose
Primary Number of Participants With One or More Adverse Events An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Up to 21 days post-dose
Secondary Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine AUC0-168hr. 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Secondary Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine Cmax. 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Secondary Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine C168hr. 168 hours after islatravir administration
Secondary Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine TMax. 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Secondary Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine apparent terminal t1/2. 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Secondary Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) Blood was collected for the determination of AUC0-168hr of islatravir in plasma. Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration. Value at 168 hours was extrapolated.
Secondary Maximum Plasma Concentration (Cmax) of Islatravir Blood was collected for the determination of Cmax of islatravir in plasma. Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Secondary Time to Maximum Plasma Concentration (Tmax) of Islatravir Blood was collected for the determination of Tmax of islatravir in plasma. Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Secondary Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma Blood was collected for the determination of apparent terminal t1/2 of islatravir in plasma. Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
See also
  Status Clinical Trial Phase
Completed NCT01968551 - Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults Phase 3
Terminated NCT03708289 - Body Composition, Bone Health and Hormonal Status in HIV-1-infected Individuals
Completed NCT02547844 - Evolution of Plasma Lipid Profile in Patients With HIV1 Who Change Atripla to Eviplera Compared to Continue With Atripla Phase 4
Terminated NCT01345630 - Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1 Phase 3
Terminated NCT01173276 - Intrauterine Insemination In HIV-Discordant Couples N/A
Completed NCT00807443 - Effect Of An Integrase Inhibitor On The Latency And Reservoir Of HIV-1 Phase 2
Completed NCT01140139 - Dermal HIV-1 Immunization During Anti-retroviral Therapy Followed by Repeated Treatment Interruptions Phase 1
Withdrawn NCT00340223 - HLA-B35 Alleles and AIDS N/A
Completed NCT00097006 - Retrovirus Epidemiology Donor Study-II (REDS-II) N/A
Completed NCT00772902 - ROCKET II - Randomized Open Label Switch for Cholesterol Elevation on Kivexa + Kaletra Evaluation Trial Phase 4
Completed NCT04006704 - Study to Assess the Acceptability of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed-Dose Combination (FDC) Tablets in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Pediatric Participants, Using Matching Placebo Tablets Phase 1
Terminated NCT03060629 - A Study to Assess the Efficacy of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa Phase 2
Recruiting NCT00981695 - Safety and Immunogenicity Study of Candidate HIV-1 Vaccine Given to Healthy Infants Born to HIV-1-infected Mothers Phase 1/Phase 2
Completed NCT01084343 - Investigation of the Safety of an HIV-1 Vaccine Given Intra-muscularly and Intra-nasally to Healthy Female Subjects Phase 1
Completed NCT00982579 - Safety and Immunogenicity Study of Candidate HIV-1 Vaccine Given to Healthy Infants Born to HIV-1/2-uninfected Mothers Phase 1
Completed NCT00665847 - TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents Phase 2
Completed NCT00098293 - Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine Phase 3
Completed NCT05944848 - A Study of CL-197 Capsules in Healthy Participants Phase 1
Completed NCT00479999 - Phase 1 Safety Study of Two Experimental HIV Vaccines Phase 1
Completed NCT01274780 - Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV-1 Infected Patients Phase 4