Single and Repeated Dose Escalation Study of GSK2838232

NCT ID: NCT02795754

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2016-12-31

Brief Summary

GSK2838232 is a Human Immunodeficiency Virus (HIV) maturation inhibitor being developed for the treatment of HIV in combination with other antiretroviral therapy (ART). The primary objectives of this study are to investigate the safety, tolerability, and pharmacokinetics (PK) of single and repeat doses of GSK2838232. This study will be a double-blind, placebo-controlled, single and repeat dose escalation study. This study will be conducted in two Parts: single escalating doses (Part 1A and 1B), and repeated escalating once daily (QD) doses for 11 days (Part 2) of GSK2838232 co-dosed with RTV. During Part 1A, single doses of GSK2838232 (as of active pharmaceutical ingredient-powder in bottle [API PiB]) 50 milligrams (mg), 100mg and 200mg will be administered with RTV. Part 1B will evaluate the relative bioavailability of single doses of crystalline active pharmaceutical ingredient (API) Immediate Release Tablet (IR) tablets versus API PiB as reference, administered with RTV. In Part 2, multiple doses of GSK2838232 will be co-administered with RTV 100mg QD for 11 days as sequential dose cohorts. Maximum duration of study participation will be approximately 10 weeks.

Conditions

Infection, Human Immunodeficiency Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GSK2838232 PIB (50 mg+100 mg+200 mg)+Placebo

During Part 1A, subjects will receive QD single dose of either GSK2838232 50 mg, 100 mg or 200 mg or placebo in each of the four visits (one treatment per visit).Subjects will also receive RTV along with all the doses and QD RTV for 48hours (2 doses) before all doses of GSK2838232 and placebo.

Group Type: EXPERIMENTAL

GSK2838232 PIB

Intervention Type: DRUG

GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

Placebo PIB

Intervention Type: DRUG

Oral suspension of hydromellulose acetate succinate will be supplied as powder-in-bottle for reconstitution.

Ritonavir

Intervention Type: DRUG

It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.

GSK2838232 PIB+IR1+IR2

During Part 1B, subjects will receive either GSK2838232 PIB, GSK2838232 IR1 or IR2 in each of the three visits (one treatment per visit) after at least 10 hours fasting and IR1 or IR2 after fat meal at visit 4.

Group Type: EXPERIMENTAL

GSK2838232 PIB

Intervention Type: DRUG

GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

GSK2838232 IR1

Intervention Type: DRUG

GSK2838232 will be available as film-coated tablet for oral use

GSK2838232 IR2

Intervention Type: DRUG

GSK2838232 will be available as film-coated tablet for oral use

Ritonavir

Intervention Type: DRUG

It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.

GSK2838232 PIB (20mg/50 mg/100 mg/200 mg)/Placebo

During Part 2, subjects will receive repeated QD doses of either GSK2838232 (20 mg, 50 mg, 100 mg or 200 mg) or placebo for 11 days. Subjects will also receive RTV along with all the doses of GSK2838232 and placebo.

Group Type: EXPERIMENTAL

GSK2838232 PIB

Intervention Type: DRUG

GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

Placebo PIB

Intervention Type: DRUG

Oral suspension of hydromellulose acetate succinate will be supplied as powder-in-bottle for reconstitution.

Ritonavir

Intervention Type: DRUG

It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.

Interventions

GSK2838232 PIB

GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

Intervention Type: DRUG

GSK2838232 IR1

GSK2838232 will be available as film-coated tablet for oral use

Intervention Type: DRUG

GSK2838232 IR2

GSK2838232 will be available as film-coated tablet for oral use

Intervention Type: DRUG

Placebo PIB

Oral suspension of hydromellulose acetate succinate will be supplied as powder-in-bottle for reconstitution.

Intervention Type: DRUG

Ritonavir

It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age: Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

Exclusion Criteria

• A creatinine clearance (CLcr) >80milliliter/minute (mL/min) as determined by Cockcroft-Gault equation CLcr (mL/min) = (140 - age) * weight (Wt) / (72 * serum creatinine [Scr]) (times 0.85 if female) where age is in years, Wt is in kilogram (kg), and Scr is in units of milligram / decilitre (mg/dL);.
• Body weight >= 50.0 kg (110 pounds [lbs.]) for men and >= 45.0kg (99lbs) for women and body mass index (BMI)
• Male or females of non-reproductive potential:

A female subject is eligible to participate if she is not pregnant [as confirmed by a negative serum human chorionic gonadotrophin (hCG) test], not lactating, and of non-reproductive potential which is defined as:

Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion ; Hysterectomy; Documented Bilateral Oophorectomy Post menopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication.

Vasectomy with documentation of azoospermia, or Male condom plus partner use of one of the contraceptive options following: Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone. Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches.

These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

• Capable of giving signed informed consent as described in Study protocol which includes compliance with the requirements and restrictions listed in the consent form and in protocol.

• Alanine aminotransferase and bilirubin >1.0* upper limit of normal (ULN).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
• Subjects who have asthma or a history of asthma.
• Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome
• 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 regular alcohol consumption within 6 months of the study defined as: For US sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
• Regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• 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 Medical Monitor, contraindicates their participation
• Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• Screening or baseline cardiac troponin I greater than the 99% cut-off (>.045 nanograms/mL by the Dimension Vista Cardiac troponin assay) for a given assay.
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• Where participation in the study would result in donation of blood or blood products in excess of 500mL within 56 days.
• 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.

Any symptomatic arrhythmia (except isolated extra systoles). Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (>=10 consecutive beats), complete heart block).

Non-sustained or sustained ventricular tachycardia (defined as >= 3 consecutive ventricular ectopic beats).

Any conduction abnormality (including but not specific to left or right incomplete or complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson White (WPW) syndrome etc.).

Sinus Pauses > 3 seconds. 300 or more supraventricular ectopic beats in 24 hours. 250 or more ventricular ectopic beats in 24 hours.

• Any clinically significant abnormal echocardiogram finding. Abnormal echocardiogram findings should be discussed with the Medical Monitor prior to enrolment.

Heart rate for Males <45 and >100 beats per minute (bpm), for females <50 and >100bpm PR Interval <120 and >220 millisecond (msec) QRS duration <70 and >120msec QT interval corrected (Fridericia's) >450msec

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

204953

Identifier Type: -

Identifier Source: org_study_id