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

Not Applicable

Completed

• Conditions: HIV; Hepatitis C
• Interventions: Drug: dolutegravir; Drug: simeprevir

• Registration Number: NCT02404805
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2015-03-18
• Study First Submitted QC: 2015-03-26
• Study First Posted: 2015-04-01
• Study Start: 2016-02
• Primary Completion: 2016-10
• Study Completion: 2016-10
• Results First Submitted: 2018-10-24
• Status Verified: 2021-02
• Results First Submitted QC: 2021-02-23
• Last Update Submitted: 2021-02-23
• Results First Posted: 2021-03-17
• Last Update Posted: 2021-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 1b	simeprevir	Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.
Sequence 3a	simeprevir	Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.
Sequence 1a	dolutegravir	Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.
Sequence 1a	simeprevir	Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.
Sequence 1b	dolutegravir	Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.
Sequence 2a	dolutegravir	Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.
Sequence 2b	dolutegravir	Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.
Sequence 2a	simeprevir	Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.
Sequence 2b	simeprevir	Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.
Sequence 3b	dolutegravir	Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.
Sequence 3a	dolutegravir	Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.
Sequence 3b	simeprevir	Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.

Primary Outcome Measures

Name	Time	Method
Simeprevir AUC Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7	Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier.
Dolutegravir AUC Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7	Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir.

Trial Locations

Locations (1)

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States