Hepatitis C, HIV
Conditions
Keywords
dolutegravir, simeprevir, HIV, HCV
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.
Interventions
DRUGdolutegravir
dolutegravir tablets 50mg, once daily x 7 days.
DRUGsimeprevir
simeprevir tablets 150mg, once daily x 7 days.
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1a Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days. | 5 |
| Sequence 1b Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days. | 3 |
| Sequence 2a Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days. | 5 |
| Sequence 2b Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days. | 5 |
| Sequence 3a Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days. | 3 |
| Sequence 3b Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days. | 4 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence 1a | Sequence 1b | Sequence 2a | Sequence 2b | Sequence 3a | Sequence 3b | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 25 Participants |
| Age, Continuous | 30.8 years | 34.3 years | 36.4 years | 35.6 years | 35.7 years | 33.8 years | 34.3 years |
| Race/Ethnicity, Customized ETHNICITY CAUCASIAN | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 22 Participants |
| Race/Ethnicity, Customized ETHNICITY HISPANIC | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United States | 5 participants | 3 participants | 5 participants | 5 participants | 3 participants | 4 participants | 25 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 4 / 25 | 7 / 24 | 10 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Dolutegravir AUC Pharmacokinetics
Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir.
Time frame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
Population: Only arms that included Dolutegravir administration are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Simeprevir Administered Alone | Dolutegravir AUC Pharmacokinetics | 68186 ng*h/mL | Geometric Coefficient of Variation 30 |
| Simeprevir and Dolutegravier Co-administered | Dolutegravir AUC Pharmacokinetics | 78433 ng*h/mL | Geometric Coefficient of Variation 24 |
Primary
Simeprevir AUC Pharmacokinetics
Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier.
Time frame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
Population: Only arms that included Simeprevir administration are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Simeprevir Administered Alone | Simeprevir AUC Pharmacokinetics | 30946 ng*h/mL | Geometric Coefficient of Variation 80 |
| Simeprevir and Dolutegravier Co-administered | Simeprevir AUC Pharmacokinetics | 30333 ng*h/mL | Geometric Coefficient of Variation 82 |