Study to Evaluate the Drug Interaction Between Dolutegravir (DTG) and Daclatasvir (DCV) in Healthy Adult Subjects

Infection, Human Immunodeficiency Virus Clinical Trial

Official title:

A Phase 1, Open-Label, Crossover Study to Evaluate the Drug Interaction Between Dolutegravir and Daclatasvir in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02082808
• Other study ID #: 201102
• Status: Completed
• Phase: Phase 1
• First received: March 6, 2014
• Last updated: June 5, 2014
• Start date: March 2014
• Est. completion date: May 2014

Study information

• Verified date: June 2014
• 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 study is designed to estimate the two-way drug interaction between DCV and DTG as a drug interaction between DTG and DCV is expected to be low and this study is to be performed as confirmation. This will be a single-center, open-label, three-period, crossover study in healthy adult subjects. This study to describe and compare steady-state plasma DTG and DCV pharmacokinetics following administration of DTG 50 mg q24h with and without DCV 60 mg q24h and following administration of DCV 60 mg q24h with and without DTG 50 mg q24h also the safety and tolerability was assessed after a repeat dose DTG 50 mg q24h with or without DCV 60 mg q24h and after a repeat dose DCV 60 mg q24h with and without DTG 50 mg q24h

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the GSK Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with serum creatinine values outside the normal range should always be excluded from enrollment.

• Body weight >=50 kg for males and 45 kg for females and BMI within the range 18.5-31.0 kg/m^2 (inclusive).

• 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 (FSH) >40 milli international unit/mL and estradiol <40 picogram/mL (<147 picomolar/L) is confirmatory.

Child-bearing potential with negative pregnancy test as determined by serum or urine hCG test at screening or prior to dosing AND Agrees to use the contraception methods 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 72 hours post the last dose.

OR has only same-sex partners, when this is her preferred and usual lifestyle.

• Male subjects with female partners of child-bearing potential must agree to use the contraception methods. This criterion must be followed from the time of the first dose of study medication until 72 hours post the last dose.

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

• Alanine aminotransferase, alkaline phosphatase and bilirubin <=1.5x upper limit of normal (ULN) (isolated bilirubin >ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• QTc <450 msec

Exclusion Criteria:

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• 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.

• 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.

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

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

• A positive pre-study drug/alcohol screen.

• A positive test for Human Immunodeficiency Virus antibody.

• Pregnant females as determined by positive serum or urine human chorionic gonadotropin test at screening or prior to dosing.

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

• Lactating females.

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• DTG
DTG is provided as 9 millimetre white, film-coated, round tablets debossed with SV 572 on one side and 50 on the other side
• DCV
DCV is provided as a plain, green, biconvex, pentagonal film-coated tablet

Locations

Country	Name	City	State
United States	GSK Investigational Site	Overland Park	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of PK parameters of DTG following DTG 50 mg q24h administration with and without DCV 60mg q24h	Plasma PK parameters for DTG include steady state area under the concentration-time curve over the dosing interval (AUC (0-tau)), maximum observed concentration (Cmax), concentration at the end of the dosing interval (Ctau), apparent clearance following oral dosing (CL/F) and terminal phase half-life (t1/2) , following DTG 50 mg q24h administration with and without DCV 60mg q24h	Day 5 in Period 1 or 2, and Period 3: pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 8, 12 and 24 hours post morning dose	No
Primary	Composite of PK parameters of DCV following administration of DCV 60 mg q24h with and without DTG 50 mg q24h	Plasma DCV steady state AUC(0-tau), Cmax, Ctau, CL/F and t1/2 following administration of DCV 60 mg q24h with and without DTG 50 mg q24h	Day 5 (Periods 1 or 2, and Period 3): pre-dose (within 15 minutes prior to dosing), 0.5,1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24hrs post morning dose	No
Secondary	Safety and Tolerability of DTG and DCV as assessed by adverse event	Safety and tolerability of repeat dose DTG 50 mg q24h with or without DCV 60 mg q24h and repeat dose DCV 60 mg q24h with and without DTG 50 mg q24h will be assessed by adverse events	Up to 36 days	No
Secondary	Safety and Tolerability of DTG and DCV as assessed by concurrent medication	Safety and tolerability of repeat dose DTG 50 mg q24h with or without DCV 60 mg q24h and repeat dose DCV 60 mg q24h with and without DTG 50 mg q24h will be assessed by concurrent medication	Up to 36 days	No
Secondary	Safety and Tolerability of DTG and DCV as assessed by clinical laboratory	Safety and tolerability of repeat dose DTG 50 mg q24h with or without DCV 60 mg q24h and repeat dose DCV 60 mg q24h with and without DTG 50 mg q24h will be assessed by clinical laboratory	Up to 36 days	No
Secondary	Safety and Tolerability of DTG and DCV as assessed by ECG	Safety and tolerability of repeat dose DTG 50 mg q24h with or without DCV 60 mg q24h and repeat dose DCV 60 mg q24h with and without DTG 50 mg q24h will be assessed by ECG	Screening	No
Secondary	Safety and Tolerability of DTG and DCV as assessed by vital signs assessments	Safety and tolerability of repeat dose DTG 50 mg q24h with or without DCV 60 mg q24h and repeat dose DCV 60 mg q24h with and without DTG 50 mg q24h will be assessed by vital signs assessments (blood pressure and heart rate)	Up to 36 days	No