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A Study of Darunavir in the Presence of Cobicistat When Administered as a Fixed Dose Combination Under Fed Conditions

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Darunavir/Cobicistat FDC
Registration Number
NCT04718805
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to evaluate the single-dose Pharmacokinetic (PK) and bioequivalence of darunavir (DRV) in the presence of cobicistat (COBI) when administered as a scored fixed dose combination (FDC) tablet (DRV/COBI) compared to the co-administration as the separate available tablet formulations (DRV and COBI), under fed conditions in healthy participants.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
Inclusion Criteria
  • Body mass index (BMI) between 18.5 and 30.0 kilograms per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg
  • Must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
  • Must be healthy on the basis of clinical laboratory tests performed at screening
  • Non-postmenopausal women must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta- hCG) 4 days or less before dosing of the first treatment period
  • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of study drug
  • Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
  • Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
  • During the study and for a minimum of at least 90 days after receiving the last dose of study drug, a male participant: must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak), must agree not to donate sperm for the purpose of reproduction
Exclusion Criteria
  • Has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
  • Has received an investigational drug or used an investigational medical device within 60 days before the first administration of the study drug
  • Has a history of hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for hepatitis A antibody IgM, HBsAg or anti-HCV at screening
  • Has previously participated in more than 3 single-dose trials or a multiple-dose trial with darunavir (DRV) and/or cobicistat (COBI)
  • Has had any contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or Coronavirus Disease 2019 (COVID-19) patients within the last 2 weeks prior to admission to the clinical research center
  • Is a woman who is pregnant, breast-feeding, or planning to become pregnant during the study or within 90 days after the last dose of study drug, or a woman of childbearing potential who is unwilling to use acceptable methods of contraception
  • Has a history of human immunodeficiency virus type 1 or type 2 (HIV-1 or HIV-2) antibody positive, or tests positive for HIV at screening
  • Positive test for SARS-CoV-2 test participants within the last 2 weeks prior to admission or during the study
  • Is a man who plans to father a child while enrolled in the study or within 90 days after the last dose of study drug, or who is unwilling to use acceptable methods of contraception

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment ADarunavirParticipants will receive Treatment A (a single dose of darunavir \[DRV\]/cobicistat \[COBI\] as one fixed dose combination \[FDC\] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence AB or BA). A washout period of at least 7 days will be maintained between each treatment period.
Treatment ADarunavir/Cobicistat FDCParticipants will receive Treatment A (a single dose of darunavir \[DRV\]/cobicistat \[COBI\] as one fixed dose combination \[FDC\] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence AB or BA). A washout period of at least 7 days will be maintained between each treatment period.
Treatment ACobicistatParticipants will receive Treatment A (a single dose of darunavir \[DRV\]/cobicistat \[COBI\] as one fixed dose combination \[FDC\] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence AB or BA). A washout period of at least 7 days will be maintained between each treatment period.
Treatment BDarunavirParticipants will receive Treatment B (a single dose of DRV/COBI as separate tablets under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence BA or AB). A washout period of at least 7 days will be maintained between each treatment period.
Treatment BCobicistatParticipants will receive Treatment B (a single dose of DRV/COBI as separate tablets under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence BA or AB). A washout period of at least 7 days will be maintained between each treatment period.
Primary Outcome Measures
NameTimeMethod
Area Under the Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of DRVPredose, up to 72 hours post dose (up to Day 4)

AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.

Maximum Observed Analyte Concentration (Cmax) of Darunavir (DRV)Predose, up to 72 hours post dose (up to Day 4)

Cmax is defined as the maximum observed analyte concentration of DRV.

Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of DRVPredose, up to 72 hours post dose (up to Day 4)

AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.

Secondary Outcome Measures
NameTimeMethod
Number of Participants with Adverse Events (AEs) as a Measure of Safety and TolerabilityUp to 6 weeks

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Cmax of Cobicistat (COBI)Predose, up to 72 hours post dose (up to Day 4)

Cmax is defined as the maximum observed analyte concentration of COBI.

Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of COBIPredose, up to 72 hours post dose (up to Day 4)

AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-BQL) concentration, calculated by linear-linear trapezoidal summation.

Area Under the Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of COBIPredose, up to 72 hours post dose (up to Day 4)

AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.

Trial Locations

Locations (1)

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

🇧🇪

Antwerpen, Belgium

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