A Healthy Volunteer And Patient Study To Assess The Safety, Tolerability And Pharmacokinetics Of GSK1265744

NCT00659191 | Completed Phase 1

• 1 other identifier: 111451
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a Phase I single and repeat dose escalation study of GSK1265744 in healthy subjects and a single repeat dose cohort in HIV-1 infected subjects. The study is planned to consist of three parts. Part A will enroll two cohorts with a total of 18 subjects in a single dose escalation to evaluate safety, tolerability and PK. Part B plans to enroll three cohorts of 10 subjects to evaluate repeat doses of GSK126744 on safety, tolerability and PK. Part A and B will enroll healthy volunteers. Part C will enroll HIV-1 patients in a single cohort of 10 subjects. This cohort will evaluate the effects of repeat dose on safety, tolerability, PK and efficacy.

Conditions

HIV Infection

Keywords

Healthy volunteer,; HIV infected subjects

Outcome Measures

Primary Outcomes (1)

• Safety evaluations (labs, ECG, blood pressure), and blood sampling for PK, Continuous AE monitoring through study conclusion and follow up, 7-14 days after last dose. For Part C only: anti-viral activity through study conclusion and follow-up.

  through study conclusion and follow up, 7-14 days after last dose

Secondary Outcomes (3)

• GSK1265744 blood levels to determine PK parameters

  on days 1 through day 10

• Plasma HIV-1 RNA levels

  from baseline and at intervals to Day 21

• To assess the development of genotypic viral resistance, if appropriate, in HIV cohort.

Interventions

GSK1265744 DRUG

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Parts A and B: The subject is healthy. Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 55 years of age.
• A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
• \- Is pre-menopausal with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy, or Is post-menopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone (FSH) level will be performed to confirm a post-menopausal status. For this study, FSH levels \> 40 mlU/ml is confirmatory.
• A male is eligible to enter and participate in the study if he is surgically sterile OR if he either agrees to abstain from sexual intercourse with a female partner or agrees to use a condom/spermicide, in addition to having his female partner use another form of contraception as in protocol
• Body weight \>/ 50 kg (110 lbs.) for men and \>/ 45 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
• A signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.
• Subject must be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Part C: HIV-infected cohort only: CD4 cell count \>/ 200 cells/mm3 and plasma HIV-1 RNA \>/ 5,000 copies/mL.
• Part C: HIV-infected cohort only: A pre-baseline viral load measurement will be obtained 7-14 days after the screening visit. The pre-baseline viral load must be within 0.7 log of the screening HIV-1 RNA and must meet the screening HIV-1 RNA (i.e., \> 5000) requirements for the subject to be included.

You may not qualify if:

• As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
• Has a positive pre-study Hepatitis B surface antigen; positive hepatitis C (HCV) antibody or detectable HCV ribonucleic acid (RNA); or positive HIV-1 antibody result. NOTE that a positive HIV-1 antibody result is acceptable for those entering the study as a subject infected with HIV-1 (Part C)
• Has a history of regular alcohol consumption averaging \>7 drinks/week for women or \>14 drinks/week for men within 6 months of the screening visit.
• Note: 1 drink is equivalent to 12 g alcohol = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
• Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
• The subject has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Participation in the study would result in donation of blood in excess of 500 mL within a 56 day period.
• Note: This does not include plasma donation.
• History or presence of allergy or intolerance to the study drug or its components or drugs of its class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• Note: "Study" or "investigational" drugs include GSK1265744 or placebo.
• Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy should be excluded.
• Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization).
• Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block \[2nd degree or higher\], WPW syndrome).
• Sinus Pauses \> 3 seconds.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Fort Lauderdale, Florida, 33306, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Orlando, Florida, 32804, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• GSK Clinical Trials, MD

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 10, 2008
• First Posted: April 16, 2008
• Study Start: February 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: October 15, 2010

Record last verified: 2010-10

Locations

US (5)