Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability, and Effects of MK-0974 (Telcagepant) on Exercise Tolerance in Patients With Stable Angina (MK-0974-014) (NCT NCT01294709)

Results Overview

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A clinical AE was an AE reported as a result of a clinical examination or reported by the participant.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

64 participants

Primary outcome timeframe

Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2

Results posted on

2018-10-18

Participant Flow

Participant milestones

Participant milestones
Measure	Telcagepant Then Placebo Participants receive single oral dose of 600 mg (two 300 mg capsules or two bioequivalent 280 mg tablets) or 900 mg telcagepant (three 300 mg capsules) in Period 1 and single oral dose of two capsules or tablets of placebo for telcagepant (or three capsules of placebo for telcagepant) in Period 2 of the crossover. Each treatment period is separated by a washout of 96-240 hours.	Placebo Then Telcagepant Participants receive single oral dose of two capsules or tablets of placebo for telcagepant (or three capsules of placebo for telcagepant) in Period 1 and a single oral dose of 600 mg (two 300 mg capsules or two bioequivalent 280 mg tablets) or 900 mg telcagepant (three 300 mg capsules) in Period 2 of the crossover. Each treatment period is separated by a washout of 96-240 hours.
Period 1 STARTED	31	33
Period 1 COMPLETED	30	32
Period 1 NOT COMPLETED	1	1
Washout Period STARTED	30	32
Washout Period COMPLETED	29	31
Washout Period NOT COMPLETED	1	1
Period 2 STARTED	29	31
Period 2 COMPLETED	28	31
Period 2 NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Assess the Safety, Tolerability, and Effects of MK-0974 (Telcagepant) on Exercise Tolerance in Patients With Stable Angina (MK-0974-014)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Enrolled Participants n=64 Participants All enrolled participants who recieved at least one dose of either telcagepant or placebo.
Age, Continuous	63.5 years FULL_RANGE 10.38 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2

Population: Safety Population which consisted of all enrolled participants who actually received assigned study drug in a particular period . Adverse events are reported by dose taken in a given treatment period and not by randomly assigned treatment sequence.

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A clinical AE was an AE reported as a result of a clinical examination or reported by the participant.

Outcome measures

Outcome measures
Measure	Telcagepant (600 mg) n=46 Participants Participants who received a single oral dose of 600 mg telcagepant capsules (or 560 mg of bioequivalent tablets) in Period 1 or 2 of crossover	Telcagepant (900 mg) n=16 Participants Participants who received a single oral dose of 900 mg telcagepant in Period 1 or 2 of crossover	Placebo n=62 Participants Participants who received a single oral dose of placebo in Period 1 or 2 of crossover
Number of Participants With Clinical Adverse Events (AEs)	7 Participants	1 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2

Population: Safety Population which consisted of all enrolled participants who actually received assigned study drug in a particular period . Adverse events are reported by dose taken in a given treatment period and not by randomly assigned treatment sequence.

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test.

Outcome measures

Outcome measures
Measure	Telcagepant (600 mg) n=46 Participants Participants who received a single oral dose of 600 mg telcagepant capsules (or 560 mg of bioequivalent tablets) in Period 1 or 2 of crossover	Telcagepant (900 mg) n=16 Participants Participants who received a single oral dose of 900 mg telcagepant in Period 1 or 2 of crossover	Placebo n=62 Participants Participants who received a single oral dose of placebo in Period 1 or 2 of crossover
Number of Participants With Laboratory Adverse Events	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2.5 to approximately 2.75 hours post dose of each treatment period

Population: Enrolled participants with evaluable treadmill exercise duration data available. Data from the 600 and 900 mg telcagepant treatments were grouped for comparsion to placebo.

Bruce (and Modified Bruce) Protocol was used to assess the exercise duration on a treadmill. This protocol consists of a standardized gradual incremental increase in external workload every 3 minutes while the participant's electrocardiogram (ECG), symptoms, and arm blood pressure were continuously monitored. Regardless of whether the participant believed he or she could continue, the test was discontinued upon evidence of chest discomfort, severe shortness of breath, dizziness, fatigue, ST-segment depression of greater than 2 mm, a fall in systolic blood pressure exceeding 10 mmHg, or the development of a ventricular tachyarrhythmia

Outcome measures

Outcome measures
Measure	Telcagepant (600 mg) n=60 Participants Participants who received a single oral dose of 600 mg telcagepant capsules (or 560 mg of bioequivalent tablets) in Period 1 or 2 of crossover	Telcagepant (900 mg) n=58 Participants Participants who received a single oral dose of 900 mg telcagepant in Period 1 or 2 of crossover	Placebo Participants who received a single oral dose of placebo in Period 1 or 2 of crossover
Total Exercise Duration on the Treadmill Test	405.38 Seconds Interval 375.91 to 434.85	412.28 Seconds Interval 382.72 to 441.85	—

SECONDARY outcome

Timeframe: 2.5 to approximately 2.75 hours post dose of each treatment period

Population: Enrolled participants with evaluable data for assessment of ST segment depression at peak exercise available. Data from the 600 and 900 mg telcagepant treatments were grouped for comparsion to placebo.

Bruce (and Modified Bruce) Protocol was used to assess the exercise duration on a treadmill. This protocol consists of a standardized gradual incremental increase in external workload every 3 minutes while the participant's ECG, symptoms, and arm blood pressure were continuously monitored. The time of peak exercise was considered the time at which the participant reached at least one of the criteria for stopping the treadmill test (evidence of chest discomfort, severe shortness of breath, dizziness, fatigue, ST-segment depression of greater than 2 mm, a fall in systolic blood pressure exceeding 10 mmHg, or the development of a ventricular tachyarrhythmia). The ECG for that timepoint (time of peak exercise) was evaluated and the amount of ST segment depression was determined.

Outcome measures

Outcome measures
Measure	Telcagepant (600 mg) n=57 Participants Participants who received a single oral dose of 600 mg telcagepant capsules (or 560 mg of bioequivalent tablets) in Period 1 or 2 of crossover	Telcagepant (900 mg) n=55 Participants Participants who received a single oral dose of 900 mg telcagepant in Period 1 or 2 of crossover	Placebo Participants who received a single oral dose of placebo in Period 1 or 2 of crossover
ST Segment Depression at Peak Exercise	-1.91 mm Interval -2.13 to -1.7	-1.86 mm Interval -2.08 to -1.64	—

SECONDARY outcome

Timeframe: 2.5 to approximately 2.75 hours post dose of each treatment period

Population: Enrolled participants with evaluable data for assessment of time to 1 mm ST segment depression available. Data from the 600 and 900 mg telcagepant treatments were grouped for comparsion to placebo.

Bruce (and Modified Bruce) Protocol was used to assess the exercise duration on a treadmill. This protocol consists of a standardized gradual incremental increase in external workload every 3 minutes while the participant's ECG, symptoms, and arm blood pressure were continuously monitored. The ECG was reviewed and the time to the first ST segment depression of 1 mm was recorded.

Outcome measures

Outcome measures
Measure	Telcagepant (600 mg) n=57 Participants Participants who received a single oral dose of 600 mg telcagepant capsules (or 560 mg of bioequivalent tablets) in Period 1 or 2 of crossover	Telcagepant (900 mg) n=56 Participants Participants who received a single oral dose of 900 mg telcagepant in Period 1 or 2 of crossover	Placebo Participants who received a single oral dose of placebo in Period 1 or 2 of crossover
Time to 1 mm ST Segment Depression	363.53 seconds Interval 330.78 to 396.27	370.67 seconds Interval 337.85 to 403.49	—

Adverse Events

Telcagepant (600 mg)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Telcagepant (900 mg)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Telcagepant (600 mg) n=46 participants at risk Participants who received a single oral dose of 600 mg telcagepant capsules (or 560 mg of bioequivalent tablets) in Period 1 or 2 of crossover	Telcagepant (900 mg) n=16 participants at risk Participants who received a single oral dose of 900 mg telcagepant in Period 1 or 2 of crossover	Placebo n=62 participants at risk Participants who received a single oral dose of placebo in Period 1 or 2 of crossover
General disorders Feeling Jittery	0.00% 0/46 • Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2 AEs are reported by dose taken in a given treatment period and not by randomly assigned treatment sequence.	6.2% 1/16 • Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2 AEs are reported by dose taken in a given treatment period and not by randomly assigned treatment sequence.	0.00% 0/62 • Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2 AEs are reported by dose taken in a given treatment period and not by randomly assigned treatment sequence.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publications derived from this study should include input from the investigator(s), and SPONSOR personnel. The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER