Bioavailability of Doravirine (MK-1439) Experimental Nano... | NCT02549040

NCT02549040

ID	Type	Description	Link
2015-002702-36	EudraCT Number
MK-1439-046	Other Identifier	Merck Protocol Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Doravirine fixed sequence treatment	Experimental	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 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)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Treatment A: Doravirine 100 mg film coated tablet	Drug	Single doravirine 100 mg film coated tablet administered orally at the start of Period 2	Doravirine fixed sequence treatment

Outcomes Module

Primary Outcomes

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.

Secondary Outcomes

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

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG00016

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00028.6± 34.6 OG00131.9± 33.9 OG00235.5± 29.6 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Comparison of Treatment B: MK-1439 150 mg tablet (40% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet					Geometric mean ratio	0.96			2-Sided	90	0.85	1.09					Other
OG001 OG002	Comparison of Treatment C: MK-1439 150 mg tablet (30% drug loaded granule) vs. Treatment A: MK-1439 100 mg film coated tablet

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.

Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.

Posted

Geometric Mean

Geometric Coefficient of Variation

μM*h

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

ID	Title	Description
OG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1
OG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2
OG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3

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.

Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.

Posted

Geometric Mean

Geometric Coefficient of Variation

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

ID	Title	Description
OG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1
OG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2
OG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3

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.

Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.

Posted

Geometric Mean

Geometric Coefficient of Variation

Periods 1 to 5: 24 hours post-dose

ID	Title	Description
OG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1
OG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2
OG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3

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.

All participants who received at least 1 administration of the trial drug.

Posted

Count of Participants

Participants

Up to 16 days after last dose of study treatment (up to approximately 92 days)

ID	Title	Description
OG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1
OG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2
OG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3

Primary

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event

All participants who received at least 1 administration of the trial drug.

Posted

Count of Participants

Participants

Up to 4 days after last dose of study treatment (up to approximately 76 days)

ID	Title	Description
OG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1
OG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2
OG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3

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.

Participants who complied with the protocol sufficiently to ensure that the data exhibited the effects of treatment, according to the underlying scientific model.

Posted

Geometric Mean

Geometric Coefficient of Variation

µM*h

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

ID	Title	Description
OG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1
OG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2
OG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Treatment B: MK-1439 150 mg Tablet (40% Drug Loaded Granule)	Participants received a single MK-1439 Type 1 dose (150 mg tablet [40% drug loaded granule]) administered orally at the start of Period 1	16	16	2	16
EG001	Treatment A: MK-1439 100 mg Film Coated Tablet	Participants received a single MK-1439 100 mg film coated tablet administered orally at the start of Period 2	16	16	5	16
EG002	Treatment C: MK-1439 150 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 2 dose (150 mg tablet [30% drug loaded granule]) administered orally at the start of Period 3	16	16	4	16
EG003	Treatment D: MK-1439 150 mg Tablet (50% Drug Loaded Granule)	Participants received a single MK-1439 Type 3 dose (150 mg tablet [50% drug loaded granule]) administered orally at the start of Period 4	16	16	6	16
EG004	Treatment E: MK-1439 100 mg Tablet (30% Drug Loaded Granule)	Participants received a single MK-1439 Type 4 dose (100 mg tablet [30% drug loaded granule]) administered orally at the start of Period 5	16	16	1	16

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vision blurred	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected16 at risk EG0020 events0 affected16 at risk EG0030 events0 affected16 at risk EG0040 events0 affected16 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0021 events1 affected16 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected16 at risk EG0020 events0 affected16 at risk EG003
Feeling of body temperture change	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0020 events0 affected16 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected16 at risk EG0020 events0 affected16 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0022 events2 affected16 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0020 events0 affected16 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0020 events0 affected16 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected16 at risk EG0022 events2 affected16 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected16 at risk EG0020 events0 affected16 at risk EG003
Menstrual discomfort	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0020 events0 affected16 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected16 at risk EG0020 events0 affected16 at risk EG003
Hot flush	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected16 at risk EG0020 events0 affected16 at risk EG003

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp.	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

ID	Term
C000592662	doravirine
D013607	Tablets

EG0041 events1 affected16 at risk

EG0040 events0 affected16 at risk

ID	Term
D004304	Dosage Forms
D004364	Pharmaceutical Preparations