Human Immunodeficiency Virus-1 (HIV-1)
Conditions
Brief summary
This study aims to evaluate and compare the relative bioavailability of different doravirine (MK-1439) experimental nano formulations (NFs) with that of a doravirine film coated tablet.
Interventions
DRUGTreatment A: Doravirine 100 mg film coated tablet
Single doravirine 100 mg film coated tablet administered orally at the start of Period 2
DRUGTreatment B: Doravirine 150 mg tablet (40% drug loaded granule)
Single doravirine NF Type 1 dose (150 mg tablet \[40% drug loaded granule\]) administered orally at the start of Period 1
DRUGTreatment C: Doravirine 150 mg tablet (30% drug loaded granule)
Single doravirine NF Type 2 dose (150 mg tablet \[30% drug loaded granule\])administered orally at the start of Period 3
DRUGTreatment D: Doravirine 150 mg tablet (50% drug loaded granule)
Single doravirine NF Type 3 dose (150 mg tablet \[50% drug loaded granule\])administered orally at the start of Period 4
DRUGTreatment E: Doravirine 100 mg tablet (30% drug loaded granule)
Single doravirine NF Type 4 dose (100 mg tablet \[30% drug loaded granule\]) administered orally at the start of Period 5
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy participants * have been a non-smoker and/or have not used nicotine or nicotine-containing products for at least approximately 3 months
Exclusion criteria
* is a pregnant or a nursing female * has a history of stroke, chronic seizures or major neurological disorder * has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases * has a history of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439 | Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose | During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose to determine Cmax after a single administration of MK-1439. |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439 | Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose | During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose to determine AUC0-inf after a single administration of MK-1439. |
| Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439 | Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose | During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose to determine AUC0-last after a single administration of MK-1439. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | Up to 4 days after last dose of study treatment (up to approximately 76 days) | An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
| Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439 | Periods 1 to 5: 24 hours post-dose | During each of the 5 treatment periods, blood samples were collected 24 hours after dosing to determine C24hr after a single administration of MK-1439. |
| Number of Participants Who Experienced at Least One Adverse Event | Up to 16 days after last dose of study treatment (up to approximately 92 days) | An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439 | Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, and 48 hours post-dose | During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48 hours after dosing to determine AUC0-48hr after a single administration of MK-1439. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-1439 Fixed Sequence Treatment After a minimum 10 hour overnight fast, participants received a single oral dose during each of 5 periods. During Period 1, participants received Treatment B: MK-1439 Type 1 dose (150 mg tablet \[40% drug loaded granule\]). During Period 2, participants received Treatment A: MK-1439 100 mg film coated tablet. During Period 3, participants received Treatment C: MK-1439 Type 2 dose (150 mg tablet \[30% drug loaded granule\]). During Period 4, participants received Treatment D: MK-1439 Type 3 dose (150 mg tablet \[50% drug loaded granule\]. During Period 5, participants received Treatment E: MK-1439 Type 4 dose (100 mg tablet \[30% drug loaded granule\]). Each period was separated by a 14 day washout. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | MK-1439 Fixed Sequence Treatment |
|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 9.48 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 16 | 5 / 16 | 4 / 16 | 6 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439
During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose to determine AUC0-inf after a single administration of MK-1439.
Time frame: Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose
Population: Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model. Participants were excluded from descriptive statistics for AUC0-inf if there were insufficient data in the terminal phase to characterize half-life (t1/2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439 | 28.6 µM*h | Geometric Coefficient of Variation 34.6 |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439 | 31.9 µM*h | Geometric Coefficient of Variation 33.9 |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439 | 35.5 µM*h | Geometric Coefficient of Variation 29.6 |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439 | 29.1 µM*h | Geometric Coefficient of Variation 30.3 |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1439 Following a Single Administration of MK-1439 | 28.0 µM*h | Geometric Coefficient of Variation 27.5 |
Comparison: Comparison of Treatment B: MK-1439 150 mg tablet (40% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.85, 1.09]
Comparison: Comparison of Treatment C: MK-1439 150 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [1.02, 1.26]
Comparison: Comparison of Treatment D: MK-1439 150 mg tablet (50% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.88, 1.11]
Comparison: Comparison of Treatment E: MK-1439 100 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.8, 0.99]
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439
During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose to determine AUC0-last after a single administration of MK-1439.
Time frame: Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose
Population: Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439 | 26.3 μM*h | Geometric Coefficient of Variation 29.3 |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439 | 29.9 μM*h | Geometric Coefficient of Variation 31.1 |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439 | 32.7 μM*h | Geometric Coefficient of Variation 26.3 |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439 | 27.0 μM*h | Geometric Coefficient of Variation 28.4 |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to Last Time (AUC0-last) With Quantifiable MK-1439 Following a Single Administration of MK-1439 | 26.3 μM*h | Geometric Coefficient of Variation 27 |
Comparison: Comparison of Treatment B: MK-1439 150 mg tablet (40% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.79, 0.98]
Comparison: Comparison of Treatment C: MK-1439 150 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.98, 1.21]
Comparison: Comparison of Treatment D: MK-1439 150 mg tablet (50% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.81, 1]
Comparison: Comparison of Treatment E: MK-1439 100 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.79, 0.97]
Primary
Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439
During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose to determine Cmax after a single administration of MK-1439.
Time frame: Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48, and 72 hours post-dose
Population: Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439 | 1070 nM | Geometric Coefficient of Variation 26.5 |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439 | 1520 nM | Geometric Coefficient of Variation 32.5 |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439 | 1320 nM | Geometric Coefficient of Variation 27.8 |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439 | 1060 nM | Geometric Coefficient of Variation 27 |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Maximum Plasma Concentration (Cmax) of MK-1439 Following a Single Administration of MK-1439 | 1160 nM | Geometric Coefficient of Variation 24.2 |
Comparison: Comparison of Treatment B: MK-1439 150 mg tablet (40% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.61, 0.82]
Comparison: Comparison of Treatment C: MK-1439 150 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.75, 1.01]
Comparison: Comparison of Treatment D: MK-1439 150 mg tablet (50% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.6, 0.81]
Comparison: Comparison of Treatment E: MK-1439 100 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.66, 0.86]
Primary
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Up to 4 days after last dose of study treatment (up to approximately 76 days)
Population: All participants who received at least 1 administration of the trial drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event
An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Up to 16 days after last dose of study treatment (up to approximately 92 days)
Population: All participants who received at least 1 administration of the trial drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Number of Participants Who Experienced at Least One Adverse Event | 2 Participants |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Number of Participants Who Experienced at Least One Adverse Event | 5 Participants |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Number of Participants Who Experienced at Least One Adverse Event | 4 Participants |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Number of Participants Who Experienced at Least One Adverse Event | 6 Participants |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
Primary
Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439
During each of the 5 treatment periods, blood samples were collected 24 hours after dosing to determine C24hr after a single administration of MK-1439.
Time frame: Periods 1 to 5: 24 hours post-dose
Population: Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439 | 395 nM | Geometric Coefficient of Variation 31.9 |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439 | 483 nM | Geometric Coefficient of Variation 33.3 |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439 | 508 nM | Geometric Coefficient of Variation 23.2 |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439 | 412 nM | Geometric Coefficient of Variation 28 |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Plasma Concentration of MK-1439 at 24 Hours Post-dose (C24hr) Following a Single Administration of MK-1439 | 402 nM | Geometric Coefficient of Variation 32 |
Comparison: Comparison of Treatment B: MK-1439 150 mg tablet (40% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.72, 0.93]
Comparison: Comparison of Treatment C: MK-1439 150 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.94, 1.18]
Comparison: Comparison of Treatment D: MK-1439 150 mg tablet (50% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.76, 0.96]
Comparison: Comparison of Treatment E: MK-1439 100 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.74, 0.94]
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439
During each of the 5 treatment periods, blood samples were collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 48 hours after dosing to determine AUC0-48hr after a single administration of MK-1439.
Time frame: Periods 1 to 5 at the following time points: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, and 48 hours post-dose
Population: Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439 | 22.8 µM*h | Geometric Coefficient of Variation 27.5 |
| Treatment A: MK-1439 100 mg Film Coated Tablet | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439 | 27.2 µM*h | Geometric Coefficient of Variation 29.2 |
| Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439 | 28.8 µM*h | Geometric Coefficient of Variation 24.8 |
| Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439 | 23.2 µM*h | Geometric Coefficient of Variation 27.3 |
| Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule) | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48 hr) Post-dose of MK-1439 Following a Single Administration of MK-1439 | 23.3 µM*h | Geometric Coefficient of Variation 25.9 |
Comparison: Comparison of Treatment B: MK-1439 150 mg tablet (40% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.75, 0.94]
Comparison: Comparison of Treatment C: MK-1439 150 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.95, 1.18]
Comparison: Comparison of Treatment D: MK-1439 150 mg tablet (50% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.76, 0.95]
Comparison: Comparison of Treatment E: MK-1439 100 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet90% CI: [0.77, 0.96]