Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/HCV Seronegative Volunteers

NCT ID: NCT02404805

Last Updated: 2021-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2016-10-31

Brief Summary

The investigator believes simeprevir concentrations are unchanged when administered in combination with dolutegravir relative to administration alone. The investigator believes dolutegravir concentrations are unchanged when administered in combination with simeprevir. Additionally, the investigator believes simeprevir and dolutegravir are safe when administered alone and in combination.

Detailed Description

To investigate the potential for drug interactions between simeprevir and dolutegravir, participants will receive each drug alone and the drugs in combination for 7 days. The pharmacokinetics of simeprevir and dolutegravir when given in combination vs. alone will be compared.

Conditions

HIV; Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Sequence 1a

Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

dolutegravir tablets 50mg, once daily x 7 days.

simeprevir

Intervention Type: DRUG

simeprevir tablets 150mg, once daily x 7 days.

Sequence 1b

Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

dolutegravir tablets 50mg, once daily x 7 days.

simeprevir

Intervention Type: DRUG

simeprevir tablets 150mg, once daily x 7 days.

Sequence 2a

Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

dolutegravir tablets 50mg, once daily x 7 days.

simeprevir

Intervention Type: DRUG

simeprevir tablets 150mg, once daily x 7 days.

Sequence 2b

Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

dolutegravir tablets 50mg, once daily x 7 days.

simeprevir

Intervention Type: DRUG

simeprevir tablets 150mg, once daily x 7 days.

Sequence 3a

Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

dolutegravir tablets 50mg, once daily x 7 days.

simeprevir

Intervention Type: DRUG

simeprevir tablets 150mg, once daily x 7 days.

Sequence 3b

Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

dolutegravir tablets 50mg, once daily x 7 days.

simeprevir

Intervention Type: DRUG

simeprevir tablets 150mg, once daily x 7 days.

Interventions

dolutegravir

dolutegravir tablets 50mg, once daily x 7 days.

Intervention Type: DRUG

simeprevir

simeprevir tablets 150mg, once daily x 7 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Men and women ages 18-60 years
• Absence of HIV-1 and HCV antibodies at screening,
• Ability and willingness to give written informed consent before the first trial-related activity.

Exclusion Criteria

• Pregnancy
• Breastfeeding
• Active alcohol or drug abuse that, in the opinion of the investigators, would interfere with adherence to study requirements
• Participation in any investigational drug study within 30 days prior to study entry
• Currently active or chronic gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease or malignancy requiring pharmacologic treatment, and/or if in the opinion of the investigator, would affect study participation, safety, or integrity of results
• Use of concomitant medication, including investigational, prescription, and over-the-counter products and dietary supplements with the following exceptions: aspirin, acetaminophen, ibuprofen, hormonal oral contraceptives
• Concomitant medications other than those listed above must have been discontinued at least 14 days before study entry
• Currently active dermatitis or urticaria or diagnosis of eczema or psoriasis,
• History of significant drug allergy (i.e., anaphylaxis and/or angioedema)
• Subjects with the following laboratory abnormalities at screening as defined by the 2004 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events ("DAIDS grading table") and in accordance with the normal ranges of the trial clinical laboratory: serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range (ULN)); hemoglobin grade 1 or greater (≤ 10.9 g/dL); platelet count grade 1 or greater (≤ 124.999 x 109/L); absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN); total bilirubin grade 1 or greater (≥ 1.1 x ULN), any other laboratory abnormality of grade 2 or above.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer J Kiser, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

References

MacBrayne CE, Castillo-Mancilla J, Burton JR Jr, MaWhinney S, Wagner CB, Micke K, Fey J, Huntley RT, Larson B, Bushman LR, Kiser JJ. Small increase in dolutegravir trough, but equivalent total dolutegravir exposure with simeprevir in HIV/HCV seronegative volunteers. J Antimicrob Chemother. 2018 Jan 1;73(1):156-159. doi: 10.1093/jac/dkx344.

Reference Type: DERIVED

PMID: 29029135 (View on PubMed)

Other Identifiers

152252

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

15-0106

Identifier Type: -

Identifier Source: org_study_id