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

NCT02404805 | Completed Results

• 2 other identifiers: 15-0106152252
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV; Hepatitis C

Keywords

dolutegravir; simeprevir; HIV; HCV

Outcome Measures

Primary Outcomes (2)

• Simeprevir AUC Pharmacokinetics

  Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier.

  Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7

• Dolutegravir AUC Pharmacokinetics

  Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir.

  Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7

Study Arms (6)

Sequence 1a

EXPERIMENTAL

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

Drug: dolutegravir; Drug: simeprevir

Sequence 1b

EXPERIMENTAL

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

Drug: dolutegravir; Drug: simeprevir

Sequence 2a

EXPERIMENTAL

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

Drug: dolutegravir; Drug: simeprevir

Sequence 2b

EXPERIMENTAL

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

Drug: dolutegravir; Drug: simeprevir

Sequence 3a

EXPERIMENTAL

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

Drug: dolutegravir; Drug: simeprevir

Sequence 3b

EXPERIMENTAL

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

Drug: dolutegravir; Drug: simeprevir

Interventions

dolutegravir DRUG

dolutegravir tablets 50mg, once daily x 7 days.

Sequence 1a; Sequence 1b; Sequence 2a; Sequence 2b; Sequence 3a; Sequence 3b

simeprevir DRUG

simeprevir tablets 150mg, once daily x 7 days.

Sequence 1a; Sequence 1b; Sequence 2a; Sequence 2b; Sequence 3a; Sequence 3b

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• 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.

  PMID: 29029135 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

dolutegravir; Simeprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jennifer Kiser
• Organization: University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

jennifer.kiser@ucdenver.edu

(303) 724-6131

Study Officials

• Jennifer J Kiser, PharmD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: April 1, 2015
• Study Start: February 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: March 17, 2021
• Results First Posted: March 17, 2021

Record last verified: 2021-02

Locations

US (1)