Single Dose Escalation Study of GSK2838232 in Healthy Subjects

NCT01802918 | Completed Phase 1

• 1 other identifier: 116787
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

GSK2838232 is a novel human immune virus (HIV) maturation inhibitor being developed for the treatment of chronic HIV infection. This study is the first administration of GSK2838232 in humans to establish the initial safety, tolerability, and pharmacokinetic profile following single doses of GSK2838232 and to evaluate the effect of food and ritonavir (RTV) on GSK2838232 in healthy subjects. There will be 2 cohorts in this study. In Cohort 1, approximately 8 healthy subjects will be enrolled (6 active and 2 placebo) at each dose visit. There will be four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence. In Cohort 2, approximately 8 healthy subjects will be enrolled (6 active doses and 2 placebo doses at each dose visit). Cohort 2 will have four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

single dose; HIV; maturation inhibitor; GSK2838232; FTIH; healthy subjects

Outcome Measures

Primary Outcomes (16)

• Number of subjects with adverse events (AEs) as a measure of safety and tolerability in cohort 1

  AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).

  Up to 16 weeks

• Number of subjects with AEs as a measure of safety and tolerability in cohort 2.

  AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).

  Up to 12 weeks

• Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 1.

  Up to 16 weeks

• Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 2

  Up to 12 weeks

• Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 1.

  Up to 16 weeks

• Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 2.

  Up to 12 weeks

• Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 1.

  Up to 16 weeks

• Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 2

  Up to 12 weeks

• Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 1

  Vital signs include blood pressure, temperature and heart rate measurement

  Up to 16 weeks.

• Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 2.

  Vital signs include blood pressure, temperature and heart rate measurement

  Up to 12 weeks

• Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 1.

  Up to 16 weeks.

• Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 2.

  Up to 12 weeks

• Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 1.

  Up to 16 weeks.

• Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 2.

  Up to 12 weeks

• Composite of pharmacokinetics (PK) parameters following single dose administration of GSK2838232 in cohort 1

  PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinity\]), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC \[0-t\]), maximum observed concentration (Cmax), time to maximum observed concentration (Tmax), observed concentration at 24hour post-dose (C24), last observed quantifiable concentration (Ct), lag time before observation of drug concentrations in sampled matrix (tlag), terminal half-life (t1/2), and apparent oral clearance (CL/F).

  PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.

• Composite of pharmacokinetics parameters following single dose administration of GSK2838232 in cohort 2.

  PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24, Ct, tlag, t1/2 and CL/F.

  PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.

Secondary Outcomes (2)

• Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with and without food in cohort 2.

  PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.

• Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with co-administration of ritonavir in cohort 2.

  PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.

Study Arms (2)

Cohort 1

EXPERIMENTAL

Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): ABCD, BACD, BCAD, or BCDA. Where A=Placebo, B= GSK2838232 5mg, C=GSK2838232 10mg, and D=GSK2838232 20mg

Drug: GSK2838232; Drug: Placebo

Cohort 2

EXPERIMENTAL

Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV.

Drug: GSK2838232; Drug: Placebo; Drug: Ritonavir

Interventions

GSK2838232 DRUG

Bottled powder with 5, 10 and 20mg unit dose strength per single dose for re-constituted oral suspension given once daily

Cohort 1; Cohort 2

Placebo DRUG

Visually matching GSK2838232

Cohort 1; Cohort 2

Ritonavir DRUG

100mg tablets once daily for 12 days

Cohort 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinically significant 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 50 years of age inclusive, at the time of signing the informed consent. A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \>40 milli international unit \[MlU\]/milliliter \[mL\] and estradiol \<40 picogram \[pg\]/mL \[\<147 picomoles /liter\] is confirmatory).
• Body weight \>= 50 kilograms (kg) (110 pounds.) for men and \>= 45 kg (99 pounds) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter\^2 (inclusive).
• A Creatinine clearance (CLcr) \>80 mL/minute (min) as determined by Cockcroft-Gault equation. CLcr (mL/min) = (140 - age) x weight / (72 x serum creatinine \[Scr\]) (times 0.85 if female) where age is in years, weight is in kg, and Scr is in units of milligram (mg)/deciliter (dL).
• Male subjects with female partners of child-bearing potential must agree to use contraception method. This criterion must be followed from the time of the first dose of study medication until the follow up visit.
• Subject must be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \>= 1.5x Upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
• Screening or baseline cardiac troponin I greater than the 99 percent cutoff (\>.045 nanogram \[ng\]/mL by the Dimension Vista cardiac troponin I \[CTNI\] assay).
• Screening BNP greater than the upper limit of normal
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• A positive test for Human Immuno Virus antibody.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive urine or serum human chorionic gonadotropin (hCG) test at screening or prior to dosing on Day 1.
• Lactating females.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Links

• Results for study 116787 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

GSK-2838232; Ritonavir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: March 4, 2013
• Study Start: February 18, 2013
• Primary Completion: November 21, 2013
• Study Completion: November 21, 2013
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1)