Relative Bioavailability Study of a Pediatric Granule Formulation of Dolutegravir

Infections, Human Immunodeficiency Virus and Herpesviridae Clinical Trial

Official title:

Relative Bioavailability Study of a Tablet Formulation vs. Pediatric Granule Formulation of Dolutegravir 50 mg and Effect of Different Types of Water Plus Infant Formula on the Pediatric Granule Formulation in Healthy Male and Female Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01382238
• Other study ID #: 114556
• Status: Completed
• Phase: Phase 1
• First received: June 23, 2011
• Last updated: September 15, 2011
• Start date: June 2011
• Est. completion date: August 2011

Study information

• Verified date: September 2011
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Dolutegravir (DTG, GSK1349572) is an integrase inhibitor currently in Phase 3 clinical trials for the treatment of human immunodeficiency virus (HIV) infection. A granule formulation has been developed as an alternative to the current tablet formulation for administration in pediatric populations.

This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of a 50 mg granule formulation of dolutegravir when administered 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula compared to the current 50 mg tablet formulation administered with tap water. Safety evaluations and serial PK samples will be collected during each treatment period. A taste assessment of the granule will also be performed. A follow-up visit will occur 5-7 days after the last dose of study drug.

Pharmacokinetic assessments during the study will 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 within a subject across all treatments (AUC(0-t)), maximum observed concentration (Cmax), terminal phase half-life (t½), lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), concentration at 24 hours post-dose (C24), and apparent clearance following oral dosing (CL/F).

Description:

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Other known NCT identifiers

• NCT01371500

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• ALT, alkaline phosphatase and bilirubin less than or equal to 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

• Male or female between 18 and 65 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 or child-bearing potential and agrees to use an appropriate contraception method for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit.

• Body weight greater than or equal to 50 kg for males and 45 kg for females and body mass index (BMI) within the range 18.5- 31.0 kg/m2 (inclusive).

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

• The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.

• 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).

• 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.

• 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 GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

• If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.

• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks/week for men or >7 drinks/week for women. - Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.

• Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.

• Lactating females.

• Unwillingness or inability to follow the procedures outlined in the protocol.

• 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, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.

• A positive test for HIV antibody.

• History of Gilbert's disease.

• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

• The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects. A single repeat is allowed for eligibility determination.

• Exclusion criteria for screening ECG within protocol limits.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes
• Infections, Human Immunodeficiency Virus and Herpesviridae

Intervention

Drug:
• Dolutegravir 50 mg tablet
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
• Dolutegravir 50 mg oral granules
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (3)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline, Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma DTG AUC(0-infinity), AUC(0-t), and Cmax		48 hours post dose	No
Secondary	Plasma DTG t½, tlag, tmax, C24, and CL/F		48 hours post dose	No
Secondary	Safety and tolerability parameters as assessed by change from baseline in 12-lead ECG and vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests		6 weeks	No