A Study to Evaluate the Pharmacokinetics and Safety of GSK1265744 and Rilpivirine and Dolutegravir and Rilpivirine in Healthy Adult Subjects

Infections, Human Immunodeficiency Virus and Hepatitis Clinical Trial

Official title:

A Phase 1, Open-Label, Crossover Study to Evaluate the Pharmacokinetics and Safety of GSK1265744 and Rilpivirine and Dolutegravir and Rilpivirine in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01467531
• Other study ID #: 116181
• Status: Completed
• Phase: Phase 1
• First received: November 3, 2011
• Last updated: October 11, 2012
• Start date: November 2011
• Est. completion date: February 2012

Study information

• Verified date: October 2012
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This will be a single-center, two-cohort, three-period study in healthy adult subjects. Approximately 16 healthy subjects will be enrolled in Cohort 1 to provide data from 14 evaluable subjects. Approximately 12 healthy subjects will be enrolled in Cohort 2 to provide data from 10 evaluable subjects. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. There will be a washout period between Period 1 and Period 2 but no washout between Period 2 and Period 3. Day 1 of Period 3 will start the day after the last day in Period 2. The study will be conducted on an out-patient basis except for days where serial pharmacokinetic sampling and safety assessments are scheduled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• 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 clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator feels 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 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.

• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol.

• Body weight greater than or equal to 50 kg for males and 45 kg for females and 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:

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

• 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 HIV antibody.

• History of regular alcohol consumption within 6 months of the study as defined in the protocol.

• 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.

• 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.

• 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 hCG test at screening or prior to dosing.

• Lactating females.

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

• Subject is mentally or legally incapacitated.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

• History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dolutegravir
50mg q 24h
• Rlipivirine
25mg q24h
• GSK1265744
30mg q24h

Locations

Country	Name	City	State
United States	GSK Investigational Site	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Pharmacokinetic Parameters following Dolutegravir administration with and without rilpivirine	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-tau)), Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Pre-dose (trough) concentration at the end of the dosing interval (Ctau)	Cohort 1: Period 1 and 3 on Day 5: pre-dose, 1, 2, 3, 4, 8, 12 and 24 hours post dose.	No
Primary	Composite of Pharmacokinetic Parameters following GSK1265744 administration with and without rilpivirine	steady state, AUC(0-t), Cmax, tmax, and Ctau	Cohort 2: Period 2 and 3, Day 12: pre-dose, 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24hrs post dose.	No
Primary	Composite of Pharmacokinetic Parameters following rilpivirine administration with and without Dolutegravir	steady state, AUC(0-tau), Cmax, tmax, and Ctau	Cohort 1: Period 2, Day 11: pre-dose, 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24hrs post dose. Period 3: Day 5 pre-dose 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24hrs post dose	No
Primary	Composite of Pharmacokinetic Parameters following rilpivirine administration with and without GSK1265744	AUC(0-tau), Cmax, tmax, and Ctau	Cohort 2: Periods 1 and 3: Day 12: pre-dose, 1, 2, 3, 4, 8, 12 and 24hrs post dose	No
Secondary	Safety and tolerability parameters, including the collection of all adverse events	Collected from first dose to final visit.	42 days or final visit has occurred	No
Secondary	Safety and tolerability parameters, including the collection of any concurrent medication from first dose to final visit	Collected from first dose to final visit.	42 days or final visit has occurred	No
Secondary	Safety and tolerability parameters, including change from baseline in clinical laboratory tests (hematology, chemistry, urinalysis) assessments		42 days or final assessment has occurred	No
Secondary	Safety and tolerability parameters, including change from baseline in ECG assessments		42 days or final assessment has occurred	No
Secondary	Safety and tolerability parameters, including change from baseline in vital signs assessments		42 days or final assessment has occurred	No