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NCT01798849

A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)

Completed Phase 1 Results posted Last updated 22 July 2019
What this trial tests

Phase 1 trial testing MK-8892 in Pulmonary Arterial Hypertension in 25 participants. Completed in 17 July 2013.

Timeline
15 March 2013
Primary endpoint
17 July 2013
17 July 2013

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment25
Start date15 March 2013
Primary completion17 July 2013
Estimated completion17 July 2013

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 60, male only, with Pulmonary Arterial Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants Primary · up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.

GroupValue95% CI
0.5 mg MK-8892-Healthy50.0
1.0 mg MK-8892-Healthy66.7
2.0 mg MK-8892-Healthy (Pooled)50.0
4.0 mg MK-8892-Healthy100.0
6.0 mg MK-8892-Healthy100.0
9.0 mg MK-8892-Healthy83.3
12.0 mg MK-8892-Healthy100.0
14.0 mg MK-8892-Healthy100.0
Placebo-Healthy43.8
Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants Primary · up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.

GroupValue95% CI
0.5 mg MK-8892-Healthy0.0
1.0 mg MK-8892-Healthy0.0
2.0 mg MK-8892-Healthy (Pooled)0.0
4.0 mg MK-8892-Healthy0.0
6.0 mg MK-8892-Healthy0.0
9.0 mg MK-8892-Healthy0.0
12.0 mg MK-8892-Healthy0.0
14.0 mg MK-8892-Healthy0.0
Placebo-Healthy0.0
Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants Primary · Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Healthy-1.83± 1.71
1.0 mg MK-8892-Healthy-2.27± 1.69
2.0 mg MK-8892-Healthy-4.21± 1.70
4.0 mg MK-8892-Healthy-4.25± 1.71
6.0 mg MK-8892-Healthy-6.22± 1.70
9.0 mg MK-8892-Healthy-6.64± 1.69
12.0 mg MK-8892-Healthy-6.94± 1.69
14.0 mg MK-8892-Healthy-8.89± 1.70
Placebo-Healthy-1.33± 1.26
Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants Primary · up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.

GroupValue95% CI
0.5 mg MK-8892-Hypertensive50.0
1.0 mg MK-8892-Hypertensive33.3
2.0 mg MK-8892-Hypertensive66.7
6.0 mg MK-8892-Hypertensive77.8
Placebo-Hypertensive75.0
Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants Primary · up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.

GroupValue95% CI
0.5 mg MK-8892-Hypertensive0.0
1.0 mg MK-8892-Hypertensive0.0
2.0 mg MK-8892-Hypertensive0.0
6.0 mg MK-8892-Hypertensive0.0
Placebo-Hypertensive0.0
Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants Primary · Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)

Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Hypertensive-3.56± 1.87
1.0 mg MK-8892-Hypertensive-4.76± 1.85
2.0 mg MK-8892-Hypertensive-7.55± 1.85
6.0 mg MK-8892-Hypertensive-7.86± 1.59
Placebo-Hypertensive-1.22± 1.67
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants Secondary · Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

Peripheral diastolic blood pressure was measured using a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Healthy-4.34± 1.73
1.0 mg MK-8892-Healthy-2.43± 0.83
2.0 mg MK-8892-Healthy-3.69± 1.10
4.0 mg MK-8892-Healthy-4.50± 1.49
6.0 mg MK-8892-Healthy-6.56± 1.06
9.0 mg MK-8892-Healthy-7.04± 0.99
12.0 mg MK-8892-Healthy-7.35± 0.71
14.0 mg MK-8892-Healthy-9.89± 1.68
Placebo-Healthy-1.67± 0.82
Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants Secondary · Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)

Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Healthy0.46± 1.36
1.0 mg MK-8892-Healthy5.55± 1.32
2.0 mg MK-8892-Healthy4.71± 1.42
4.0 mg MK-8892-Healthy7.44± 1.93
6.0 mg MK-8892-Healthy9.29± 2.22
9.0 mg MK-8892-Healthy8.85± 1.93
12.0 mg MK-8892-Healthy10.34± 1.09
14.0 mg MK-8892-Healthy16.29± 2.21
Placebo-Healthy2.23± 1.11
Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants Secondary · Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)

AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours.

GroupValue95% CI
0.5 mg MK-8892-Healthy-1.73± 2.30
1.0 mg MK-8892-Healthy-2.31± 2.32
2.0 mg MK-8892-Healthy-2.82± 2.31
4.0 mg MK-8892-Healthy-0.26± 2.38
6.0 mg MK-8892-Healthy-4.23± 2.29
9.0 mg MK-8892-Healthy-3.85± 2.31
12.0 mg MK-8892-Healthy-1.84± 2.30
14.0 mg MK-8892-Healthy-4.81± 2.32
Placebo-Healthy-0.07± 2.06
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants Secondary · Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

Peripheral blood pressure assessments were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose by using a validated automatic measuring device. Peripheral diastolic blood pressure was measured a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Hypertensive-3.40± 1.13
1.0 mg MK-8892-Hypertensive-4.17± 1.63
2.0 mg MK-8892-Hypertensive-7.29± 1.40
6.0 mg MK-8892-Hypertensive-9.16± 1.43
Placebo-Hypertensive-0.87± 1.40
Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants Secondary · Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)

Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Hypertensive-0.92± 1.59
1.0 mg MK-8892-Hypertensive-0.74± 1.88
2.0 mg MK-8892-Hypertensive0.87± 1.92
6.0 mg MK-8892-Hypertensive7.68± 1.51
Placebo-Hypertensive-1.46± 1.62
TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants Secondary · Predose to 24 hours Postdose (for each Dosing Period of Each Panel)

AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.

GroupValue95% CI
0.5 mg MK-8892-Hypertensive-2.30± 2.01
1.0 mg MK-8892-Hypertensive-2.57± 2.01
2.0 mg MK-8892-Hypertensive-3.94± 2.01
6.0 mg MK-8892-Hypertensive-5.43± 1.80
Placebo-Hypertensive-1.65± 1.86

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 7 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

0.5 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
1.0 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
2.0 mg MK-8892-Healthy (Pooled)
Serious: 0/6 (0%)
Deaths: 0/6
4.0 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
6.0 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
9.0 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
12.0 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
14.0 mg MK-8892-Healthy
Serious: 0/6 (0%)
Deaths: 0/6
Placebo-Healthy
Serious: 0/16 (0%)
Deaths: 0/16
0.5 mg MK-8892-Hypertensive
Serious: 0/6 (0%)
Deaths: 0/6
1.0 mg MK-8892-Hypertensive
Serious: 0/6 (0%)
Deaths: 0/6
2.0 mg MK-8892-Hypertensive
Serious: 0/6 (0%)
Deaths: 0/6
6.0 mg MK-8892-Hypertensive
Serious: 0/9 (0%)
Deaths: 0/9
Placebo-Hypertensive
Serious: 0/8 (0%)
Deaths: 0/8
Other adverse events (47 terms — click to expand)

ReactionSystem0.5 mg MK-8892-Healthy1.0 mg MK-8892-Healthy2.0 mg MK-8892-Healthy (Po…4.0 mg MK-8892-Healthy6.0 mg MK-8892-Healthy9.0 mg MK-8892-Healthy12.0 mg MK-8892-Healthy14.0 mg MK-8892-HealthyPlacebo-Healthy0.5 mg MK-8892-Hypertensive1.0 mg MK-8892-Hypertensive2.0 mg MK-8892-Hypertensive6.0 mg MK-8892-HypertensivePlacebo-Hypertensive
HeadacheNervous system disorders
FatigueGeneral disorders
Orthostatic hypotensionVascular disorders
PalpitationsCardiac disorders
NauseaGastrointestinal disorders
Common coldInfections and infestations
Blood pressure systolic decreasedInvestigations
Postural orthostatic tachycardia syndromeCardiac disorders
TinnitusEar and labyrinth disorders
Abdominal discomfortGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Change of bowel habitGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Loose stoolsGastrointestinal disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
CystGeneral disorders
Feeling hotGeneral disorders
Oedema peripheralGeneral disorders
Oral herpesInfections and infestations
Lower limb woundInjury, poisoning and procedural complications
Open woundInjury, poisoning and procedural complications
Upper limb woundInjury, poisoning and procedural complications
Blood pressure systolic increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Back pain (with radiation)Musculoskeletal and connective tissue disorders
Flank painMusculoskeletal and connective tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Pain in armMusculoskeletal and connective tissue disorders
Shoulder painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Dizziness posturalNervous system disorders
PresyncopeNervous system disorders
PolyuriaRenal and urinary disorders
Urine odour abnormalRenal and urinary disorders
Bronchial hyperreactivityRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT01798849 adverse events section.

Sponsor's own description

This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

Verify or expand the search:

Other trials of MK-8892

Trials testing the same drug.

Other recruiting trials for Pulmonary Arterial Hypertension

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01798849.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing