A study to compare two pediatric formulations to the adult formulation of cobicistat 150 mg tablet in healthy adult volunteers

Conditions: Human Immunodeficiency Virus (HIV-1) Infections
MedDRA version: 17.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2015-000466-57-Outside-EU/EEA

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 60

Inclusion Criteria

1) Have the ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures
2) Must be between 18 and 45 years of age, inclusive
3) Must be a nonsmoker. The use of nicotine or nicotine-containing products must be discontinued 90 days prior to the first dose of study drug
4) Must have a calculated body mass index (BMI) from 19 = BMI = 30 at study screening
5) Must be HIV-1 antibody negative
6) Must be hepatitis B (HBV) surface antigen negative
7) Must be hepatitis C (HCV) antibody negative
8) Have an estimated creatinine clearance (CLCr) = 90 mL/min (using the Cockcroft-Gault method)
9) Females of childbearing potential must have a negative serum pregnancy test
10) Females of childbearing potential must agree to utilize protocol recommended highly effective contraception methods from 3 weeks prior to baseline throughout the duration of study treatment and for 30 days following the last dose of study drug
11) Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least 3 months prior to study dosing
12) Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
13) Male subjects must refrain from sperm donation from Day -1 through completion of the study and continuing for at least 30 days from the date of last dose of study drug
14) Subjects must refrain from blood donation from Day -1 through completion of the study and continuing for at least 30 days from date of last dose of study drug
15) Must, in the opinion of the Investigator, be in good health based upon medical history, physical examination, and screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory’s reference ranges unless the results have been determined by the Investigator to have no clinical significance. Subjects must have ALT, AST and total bilirubin within or below the normal range
16) Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the Investigator in consultation with the Sponsor. Subjects must have PR between 120 – 210 msec, and QTcF of <450 for males and <470 for females
17) Must be willing and able to comply with all study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Pregnant or lactating subjects
2) Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol
3) Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to the study dosing
4) Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance
5) Have poor venous access and are unable to donate blood
6) Have donated blood within 56 days of study dosing
7) Have donated plasma within 7 days of study dosing
8) Have taken any prescription medications or over-the-counter medications including herbal products within 28 days of commencing study drug dosing with the exception of vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications
9) Have history of significant drug sensitivity or drug allergy
10) Known hypersensitivity to the study drugs, the metabolites or formulation excipients
11) Have been treated with systemic steroids, immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
12) Have a history or family history of Long QT Syndrome, Wolfe-Parkinson-White Syndrome, or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual between the ages of 1 and 40 years
13) History of syncope, palpitations, or unexplained dizziness
14) Have an implanted defibrillator or pacemaker
15) Have a history of liver disease, including Gilbert’s Disease
16) Are unable to comply with study requirements
17) Believed, by the study Investigator, to be inappropriate for study participation for any reason

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the relative bioavailability of two age-appropriate pediatric formulations (immediate release tablet or dispersible tablet as suspension) of COBI in healthy adult subjects;Secondary Objective: To evaluate the safety of two age-appropriate pediatric formulations (immediate release tablet or dispersible tablet as suspension) of COBI in healthy adult subjects<br><br>To evaluate the acceptability of COBI formulations in healthy adult subjects;Primary end point(s): The primary endpoints are the pharmacokinetic (PK) parameters AUClast, AUCinf, and Cmax for COBI.;Timepoint(s) of evaluation of this end point: PK assessments: Days 1 and 8: serial blood samples will be collected at the following time points relative to dosing: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 20, 24, 28, 36, and 48 hours post-dose.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary endpoints are %AUC_exp, Tmax, Clast, Tlast, ?z, T1/2, clearance and volume of distribution for COBI, acceptability for COBI formulations, and incidences of adverse events and laboratory abnormalities;Timepoint(s) of evaluation of this end point: PK assessments: Days 1 and 8: serial blood samples will be collected at the following time points relative to dosing: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 20, 24, 28, 36, and 48 hours post-dose. Safety assessments, acceptability and AEs to be collected from baseline to day 15 follow-up visits.