Clinical trial NCT02404805: Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/HCV Seronegative Volunteers
Official title: Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/Hepatitis C Virus (HCV) Seronegative Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Hepatitis C
Keywords: dolutegravir
simeprevir
HIV
HCV
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-04-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Simeprevir AUC Pharmacokinetics
timeFrame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
measure: Dolutegravir AUC Pharmacokinetics
timeFrame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Jennifer J Kiser, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.