Bioavailability of Doravirine (MK-1439) Experimental Nano Formulations in Healthy Adults (MK-1439-046)

Study Overview
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Brief Summary
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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.

Official Title
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A Rapid Pharmacokinetic Trial of the Bioavailability of Four MK-1439 Nano Formulations in Healthy Adults

Conditions
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Human Immunodeficiency Virus-1 (HIV-1)

Intervention / Treatment
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* Drug: Treatment A: Doravirine 100 mg film coated tablet
* Drug: Treatment B: Doravirine 150 mg tablet (40% drug loaded granule)
* Drug: Treatment C: Doravirine 150 mg tablet (30% drug loaded granule)
* Drug: Treatment D: Doravirine 150 mg tablet (50% drug loaded granule)
* Drug: Treatment E: Doravirine 100 mg tablet (30% drug loaded granule)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doravirine fixed sequence treatment<br>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: Doravirine Type 1 dose (150 mg tablet [40% drug loaded granule]). During Period 2, participants received Treatment A: Doravirine 100 mg film coated tablet. During Period 3, participants received Treatment C: Doravirine Type 2 dose (150 mg tablet [30% drug loaded granule]). During Period 4, participants received Treatment D: Doravirine Type 3 dose (150 mg tablet [50% drug loaded granule]. During Period 5, participants received Treatment E: Doravirine Type 4 dose (100 mg tablet [30% drug loaded granule]). Each period was separated by a 14 day washout. | Drug: Treatment A: Doravirine 100 mg film coated tablet<br>* Single doravirine 100 mg film coated tablet administered orally at the start of Period 2<br>* Other names: MK-1439;Drug: Treatment B: Doravirine 150 mg tablet (40% drug loaded granule)<br>* Single doravirine NF Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1<br>* Other names: MK-1439;Drug: Treatment C: Doravirine 150 mg tablet (30% drug loaded granule)<br>* Single doravirine NF Type 2 dose (150 mg tablet [30% drug loaded granule])administered orally at the start of Period 3<br>* Other names: MK-1439;Drug: Treatment D: Doravirine 150 mg tablet (50% drug loaded granule)<br>* Single doravirine NF Type 3 dose (150 mg tablet [50% drug loaded granule])administered orally at the start of Period 4<br>* Other names: MK-1439;Drug: Treatment E: Doravirine 100 mg tablet (30% drug loaded granule)<br>* Single doravirine NF Type 4 dose (100 mg tablet [30% drug loaded granule]) administered orally at the start of Period 5<br>* Other names: MK-1439;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | Periods 1 to 5: 24 hours post-dose | 
| 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. | Up to 16 days after last dose of study treatment (up to approximately 92 days) | 
| 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. | Up to 4 days after last dose of study treatment (up to approximately 76 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 |