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

NCT02082808 | Completed Phase 1

• 1 other identifier: 201102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Infection, Human Immunodeficiency Virus

Keywords

Dolutegravir; healthy volunteer; pharmacokinetics; daclatasvir; drug interaction

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (5)

• Safety and Tolerability of DTG and DCV as assessed by adverse event

  Up to 36 days

• Safety and Tolerability of DTG and DCV as assessed by concurrent medication

  Up to 36 days

• Safety and Tolerability of DTG and DCV as assessed by clinical laboratory

  Up to 36 days

• Safety and Tolerability of DTG and DCV as assessed by ECG

  Screening

• Safety and Tolerability of DTG and DCV as assessed by vital signs assessments

  Up to 36 days

Study Arms (2)

Sequence 1

EXPERIMENTAL

Participants will receive the study Treatment A for 5 days (DTG 50mg q24h) in Period 1 followed by a washout period (\>=7days) and Treatment B for 5 days (DCV 60mg q24h) in Period 2 and Treatment C (DCV 60mg q24h + DTG 50mg q24h) for 5 days in Period 3

Drug: DTG; Drug: DCV

Sequence 2

EXPERIMENTAL

Participants will receive the study Treatment B for 5 days (DCV 60mg q24h) in Period 1 followed by a washout period (\>=7days) and Treatment A for 5 days (DTG 50mg q24h) in Period 2 and Treatment C (DCV 60mg q24h + DTG 50mg q24h) for 5 days in Period 3

Drug: DTG; Drug: DCV

Interventions

DTG DRUG

DTG is provided as 9 millimetre white, film-coated, round tablets debossed with SV 572 on one side and 50 on the other side

Sequence 1; Sequence 2

DCV DRUG

DCV is provided as a plain, green, biconvex, pentagonal film-coated tablet

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

Related Publications (1)

• Ross LL, Song IH, Arya N, Choukour M, Zong J, Huang SP, Eley T, Wynne B, Buchanan AM. No clinically significant pharmacokinetic interactions between dolutegravir and daclatasvir in healthy adult subjects. BMC Infect Dis. 2016 Jul 22;16:347. doi: 10.1186/s12879-016-1629-5.

  PMID: 27450277 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

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

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: March 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 9, 2014

Record last verified: 2014-06

Locations

US (1)