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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus-1 (HIV-1)
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Doravirine 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: 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; Single doravirine 100 mg film coated tablet administered orally at the start of Period 2; Other Names: MK-1439; Drug: Treatment 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; Other Names: MK-1439; Drug: Treatment 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; Other Names: MK-1439; Drug: Treatment 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; Other Names: MK-1439; Drug: Treatment 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; Other Names: MK-1439

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2015
• Primary Completion (Actual): December 24, 2015
• Study Completion (Actual): December 24, 2015

Study Registration Dates

• First Submitted: September 11, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): January 7, 2021
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 1439-046; 2015-002702-36 (EudraCT Number); MK-1439-046 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf