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

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Hepatitis C; HIV

Treatments: Drug: dolutegravir; Drug: simeprevir

Study type: Interventional

Funder types: Other

Identifiers

NCT02404805

15-0106

152252 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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25 participants in 6 patient groups

Sequence 1a

Experimental group

Description:

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

Treatment:

Drug: simeprevir

Drug: dolutegravir

Sequence 1b

Experimental group

Description:

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

Treatment:

Drug: simeprevir

Drug: dolutegravir

Sequence 2a

Experimental group

Description:

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

Treatment:

Drug: simeprevir

Drug: dolutegravir

Sequence 2b

Experimental group

Description:

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

Treatment:

Drug: simeprevir

Drug: dolutegravir

Sequence 3a

Experimental group

Description:

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

Treatment:

Drug: simeprevir

Drug: dolutegravir

Sequence 3b

Experimental group

Description:

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

Treatment:

Drug: simeprevir

Drug: dolutegravir