Trial Outcomes & Findings for MK0462 in Treatment of Migraine With Recurrence (MK0462-022) (NCT NCT00897949)

NCT ID: NCT00897949

Last Updated: 2022-02-03

Results Overview

Patients reporting pain relief (defined as a reduction of headache severity from grades 2/3 at baseline to 0/1) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1473 participants
• Primary outcome timeframe: 2 hours after initial dose of test drug
• Results posted on: 2022-02-03

Participant Flow

Patients were recruited at 28 sites in the United States and 18 in 9 other countries. First Patient Treated: Mar 1995 Last Patient Treated: Jan 1996.

Outpatients randomized at the prestudy visit were given study drug and administration instructions. If patients had not treated an attack within 2 months of being enrolled, they were required to return for a rescreen visit. If by 4 months after being enrolled patients still had not treated an attack, they were discontinued from the study

Participant milestones

Measure	Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment
Overall Study STARTED	554	549	370
Overall Study Patients Treated	458	456	304
Overall Study COMPLETED	450	446	301
Overall Study NOT COMPLETED	104	103	69

Reasons for withdrawal

Measure	Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment
Overall Study Adverse Event	1	1	0
Overall Study Lost to Follow-up	30	23	17
Overall Study Protocol Violation	6	3	1
Overall Study Withdrawal by Subject	24	31	17
Overall Study Patient Uncoorperative	0	2	1
Overall Study Abnormal Prestudy Labs	2	3	4
Overall Study Abnormal Baseline ECG	2	2	4
Overall Study Need for Concom. Med.	0	1	1
Overall Study Lack of Migraine Attack	29	30	19
Overall Study Did not take study drug	9	3	4

Baseline Characteristics

MK0462 in Treatment of Migraine With Recurrence (MK0462-022)

Baseline characteristics by cohort

Measure	Rizatriptan 5 mg n=458 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=456 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=304 Participants Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment	Total n=1218 Participants Total of all reporting groups
Age, Continuous	40.5 years STANDARD_DEVIATION 9.6 • n=5 Participants	40.7 years STANDARD_DEVIATION 9.6 • n=7 Participants	40.6 years STANDARD_DEVIATION 10.5 • n=5 Participants	40.6 years STANDARD_DEVIATION 9.9 • n=4 Participants
Sex: Female, Male Female	394 Participants n=5 Participants	402 Participants n=7 Participants	259 Participants n=5 Participants	1055 Participants n=4 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	54 Participants n=7 Participants	45 Participants n=5 Participants	163 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	430 participants n=5 Participants	422 participants n=7 Participants	286 participants n=5 Participants	1138 participants n=4 Participants
Race/Ethnicity, Customized Black	18 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	32 participants n=4 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	12 participants n=7 Participants	3 participants n=5 Participants	17 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Mexican-American	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Syrian	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Anglo-Asian	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Mixed	3 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	8 participants n=4 Participants
Race/Ethnicity, Customized Other	4 participants n=5 Participants	9 participants n=7 Participants	5 participants n=5 Participants	18 participants n=4 Participants
Baseline Headache Severity Grade 0, 1: No pain, Mild, or missing	8 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Baseline Headache Severity Grade 2: Moderate	298 Participants n=5 Participants	316 Participants n=7 Participants	202 Participants n=5 Participants	816 Participants n=4 Participants
Baseline Headache Severity Grade 3: Severe	152 Participants n=5 Participants	131 Participants n=7 Participants	95 Participants n=5 Participants	378 Participants n=4 Participants

PRIMARY outcome

Timeframe: 2 hours after initial dose of test drug

Population: The primary analysis employed an "all-patients-treated" approach that included all patients who had at least one record of pain severity within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.

Patients reporting pain relief (defined as a reduction of headache severity from grades 2/3 at baseline to 0/1) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain.

Outcome measures

Measure	Rizatriptan 5 mg n=457 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=455 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=302 Participants Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment	Rizatriptan 10 mg / Placebo Rizatriptan 10 mg initially, prerandomized to placebo	Placebo / Rizatriptan 5 mg Placebo initially, prerandomized to rizatriptan 5 mg	Placebo / Rizatriptan 10 mg Placebo initially, prerandomized to rizatriptan 10 mg
Pain Relief at 2 Hours After the Initial Dose of Test Drug Reporting pain relief	285 Participants	322 Participants	106 Participants	—	—	—
Pain Relief at 2 Hours After the Initial Dose of Test Drug Not reporting pain relief	172 Participants	133 Participants	196 Participants	—	—	—

SECONDARY outcome

Timeframe: 2 hours after initial dose of test drug

Population: An "all-patients-treated" approach was employed that included all patients who had at least one record of pain severity within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.

Patients reporting pain free (defined as a reduction of headache severity to grade 0 [no pain]) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain.

Outcome measures

Measure	Rizatriptan 5 mg n=457 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=455 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=302 Participants Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment	Rizatriptan 10 mg / Placebo Rizatriptan 10 mg initially, prerandomized to placebo	Placebo / Rizatriptan 5 mg Placebo initially, prerandomized to rizatriptan 5 mg	Placebo / Rizatriptan 10 mg Placebo initially, prerandomized to rizatriptan 10 mg
Pain Free at 2 Hours After the Initial Dose of Test Drug Reporting no pain	150 Participants	193 Participants	30 Participants	—	—	—
Pain Free at 2 Hours After the Initial Dose of Test Drug Reporting pain	307 Participants	262 Participants	272 Participants	—	—	—

SECONDARY outcome

Timeframe: 2 hours after initial dose of test drug

Population: An "all-patients-treated" approach was employed that included all patients who had at least one record of functional disability within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.

Patients with no disability at 2 hours after the initial dose of test drug. Functional disability was subjectively rated on a scale from grade 0 to 3: Grade 0 - Normal, Grade 1 - Daily activities mildly impaired, Grade 2 - Daily activities severely impaired, Grade 3 - Unable to carry out daily activities, requires bedrest

Outcome measures

Measure	Rizatriptan 5 mg n=457 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=454 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=300 Participants Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment	Rizatriptan 10 mg / Placebo Rizatriptan 10 mg initially, prerandomized to placebo	Placebo / Rizatriptan 5 mg Placebo initially, prerandomized to rizatriptan 5 mg	Placebo / Rizatriptan 10 mg Placebo initially, prerandomized to rizatriptan 10 mg
No Disability at 2 Hours After the Initial Dose of Test Drug Mildly Impaired	160 Participants	148 Participants	118 Participants	—	—	—
No Disability at 2 Hours After the Initial Dose of Test Drug Severely Impaired	56 Participants	45 Participants	53 Participants	—	—	—
No Disability at 2 Hours After the Initial Dose of Test Drug Requires Bedrest	66 Participants	52 Participants	75 Participants	—	—	—
No Disability at 2 Hours After the Initial Dose of Test Drug Normal	175 Participants	209 Participants	54 Participants	—	—	—

SECONDARY outcome

Timeframe: 2 hours after initial dose of test drug

Population: An "all-patients-treated" approach was employed that included all patients who had at least one record of pain severity within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.

Outcome measures

Measure	Rizatriptan 5 mg n=458 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=456 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=304 Participants Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment	Rizatriptan 10 mg / Placebo Rizatriptan 10 mg initially, prerandomized to placebo	Placebo / Rizatriptan 5 mg Placebo initially, prerandomized to rizatriptan 5 mg	Placebo / Rizatriptan 10 mg Placebo initially, prerandomized to rizatriptan 10 mg
Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug Used escape medication	101 Participants	76 Participants	128 Participants	—	—	—
Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug Did not use escape medication	357 Participants	380 Participants	176 Participants	—	—	—

SECONDARY outcome

Timeframe: 2 hours after treatment for recurrence

Population: Patients with initial headache recurrence who took rizatriptan 5 mg or 10 mg were prerandomized (ratio=1:1) to either rizatriptan 5 mg or 10 mg, respectively, or to placebo (ratio=1:1); and who took placebo, to either 5 mg or 10 mg of rizatriptan (ratio=1:1). Only those who took rizatriptan for their initial headache were considered for analysis.

Patients reporting pain relief 2 hours after treatment for headache recurrence (defined as the return of headache to grade 2 or 3 within 24 hours of the initial dose in patients who reported pain relief (grades 0 or 1) at 2 hours).

Outcome measures

Measure	Rizatriptan 5 mg n=55 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=59 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=65 Participants Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment	Rizatriptan 10 mg / Placebo n=75 Participants Rizatriptan 10 mg initially, prerandomized to placebo	Placebo / Rizatriptan 5 mg n=17 Participants Placebo initially, prerandomized to rizatriptan 5 mg	Placebo / Rizatriptan 10 mg n=22 Participants Placebo initially, prerandomized to rizatriptan 10 mg
Pain Relief 2 Hours After Treatment for Headache Recurrence Pain relief	39 Participants	32 Participants	53 Participants	33 Participants	12 Participants	18 Participants
Pain Relief 2 Hours After Treatment for Headache Recurrence No pain relief	16 Participants	27 Participants	12 Participants	42 Participants	5 Participants	4 Participants

Adverse Events

Rizatriptan 5 mg

Serious events: 3 serious events

Other events: 155 other events

Deaths: 0 deaths

Rizatriptan 10 mg

Serious events: 0 serious events

Other events: 254 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rizatriptan 5 mg n=456 participants at risk Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=455 participants at risk Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=307 participants at risk Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment
Nervous system disorders Headache	0.22% 1/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Migraine	0.44% 2/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.

Other adverse events

Measure	Rizatriptan 5 mg n=456 participants at risk Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=455 participants at risk Rizatriptan 10 mg orally once for treatment of single migraine attack	Placebo n=307 participants at risk Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment
General disorders Asthenia/Fatigue	2.6% 12/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	7.3% 33/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	2.0% 6/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
General disorders Pain, Abdominal	1.3% 6/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	2.0% 9/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.3% 4/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
General disorders Pain, Chest	1.5% 7/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	2.6% 12/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.65% 2/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Gastrointestinal disorders Dry Mouth	2.4% 11/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	3.3% 15/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.6% 5/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Gastrointestinal disorders Nausea	4.2% 19/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	4.8% 22/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	4.6% 14/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Gastrointestinal disorders Vomiting	2.0% 9/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	2.2% 10/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.3% 4/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Investigations Alanine Amino Transferase (ALT) Increased	0.66% 3/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.66% 3/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.65% 2/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Investigations Aspartate Amino Transferase (AST) Increased	0.22% 1/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.66% 3/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.65% 2/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Musculoskeletal and connective tissue disorders Tightness, Regional	0.44% 2/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.1% 5/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Disorientation	0.00% 0/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.1% 5/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Dizziness	4.2% 19/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	9.9% 45/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	4.6% 14/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Headache	1.5% 7/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.8% 8/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.65% 2/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Hypesthesia	0.88% 4/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.88% 4/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.3% 4/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Insomnia	1.1% 5/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.44% 2/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Paresthesia	2.4% 11/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	3.7% 17/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.3% 4/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Somnolence	3.5% 16/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	8.1% 37/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	2.9% 9/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Nervous system disorders Tremor	1.3% 6/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.22% 1/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.6% 5/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Discomfort, Pharyngeal	1.3% 6/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	2.2% 10/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.00% 0/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Infections and infestations Infection, Respiratory, Upper	1.1% 5/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.88% 4/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.33% 1/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Skin and subcutaneous tissue disorders Flushing	0.88% 4/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.88% 4/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.3% 4/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.
Reproductive system and breast disorders Hot Flashes	0.44% 2/456 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	1.1% 5/455 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.	0.33% 1/307 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a patient may have had two or more adverse experiences the patient is counted only once in a category. The same patient may appear in different categories. The subjects reported at risk are subjects with follow-up after at least one dose of study drug.

Additional Information

Senior Vice President,Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER