Trial Outcomes & Findings for Treatment of Multiple Attacks of Acute Migraine (0462-025) (NCT NCT00899379)

Last Updated: 2022-02-03

Results Overview

Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) at baseline to grades 0 or 1 (no headache or mild) at 2 hours after initial dosing for the first migraine attack

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

473 participants

Primary outcome timeframe

2 hours

Results posted on

2022-02-03

Participant Flow

Patients were recruited at 23 sites in the United States. First Patient Treated: April, 1995 Last Patient Treated: January 1996

Patients screened at a pretreatment visit were given allocated drug supply with instructions. If by 2 months after screening, a patient still had not treated a migraine attack with test medication, he/she was to be discontinued from the study.

Participant milestones

Participant milestones
Measure	Placebo/Rizatriptan/Rizatriptan/Rizatriptan Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Placebo/Rizatriptan/Rizatriptan Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Placebo/Rizatriptan Rizatriptan 10 mg/Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Rizatriptan/Placebo Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Placebo = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Rizatriptan/Rizatriptan Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)
Overall Study STARTED	95	95	95	94	94
Overall Study Patients Treated	83	82	84	77	81
Overall Study Patients Not Treated	12	13	11	17	13
Overall Study COMPLETED	61	66	66	57	63
Overall Study NOT COMPLETED	34	29	29	37	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Rizatriptan/Rizatriptan/Rizatriptan Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Placebo/Rizatriptan/Rizatriptan Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Placebo/Rizatriptan Rizatriptan 10 mg/Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Rizatriptan/Placebo Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Placebo = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Rizatriptan/Rizatriptan Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)
Overall Study Adverse Event	2	2	1	1	2
Overall Study Lack of Efficacy	0	4	3	0	1
Overall Study Lost to Follow-up	3	1	0	2	5
Overall Study Protocol Violation	0	0	1	1	0
Overall Study Withdrawal by Subject	4	7	4	7	2
Overall Study Pregnancy	1	0	0	0	0
Overall Study Patient Uncooperative	0	0	0	1	0
Overall Study Abnormal Baseline ECG	0	0	1	1	0
Overall Study No Longer Met Inc/Exc Criteria	1	0	0	0	0
Overall Study Not Completed/Entered Extn	5	1	6	4	3
Overall Study Study Terminated	3	0	3	3	1
Overall Study Abnormal Prestudy Labs	0	0	0	0	2
Overall Study No Attack Pretreatment	3	5	5	6	4
Overall Study Inc/Exc Criteria Not Met	0	0	1	0	0

Baseline Characteristics

Treatment of Multiple Attacks of Acute Migraine (0462-025)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Rizatriptan/Rizatriptan/Rizatriptan n=83 Participants Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Placebo/Rizatriptan/Rizatriptan n=82 Participants Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Placebo/Rizatriptan n=84 Participants Rizatriptan 10 mg/Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Rizatriptan/Placebo n=77 Participants Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Placebo = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Rizatriptan/Rizatriptan/Rizatriptan/Rizatriptan n=81 Participants Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches)	Total n=407 Participants Total of all reporting groups
Age, Continuous	41.1 years STANDARD_DEVIATION 9.6 • n=5 Participants	41.0 years STANDARD_DEVIATION 9.8 • n=7 Participants	42.3 years STANDARD_DEVIATION 10.6 • n=5 Participants	39.5 years STANDARD_DEVIATION 10.1 • n=4 Participants	38.9 years STANDARD_DEVIATION 10.8 • n=21 Participants	40.6 years STANDARD_DEVIATION 10.2 • n=8 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	71 Participants n=7 Participants	72 Participants n=5 Participants	63 Participants n=4 Participants	67 Participants n=21 Participants	341 Participants n=8 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	14 Participants n=21 Participants	66 Participants n=8 Participants
Race/Ethnicity, Customized Caucasian	76 participants n=5 Participants	75 participants n=7 Participants	80 participants n=5 Participants	72 participants n=4 Participants	79 participants n=21 Participants	382 participants n=8 Participants
Race/Ethnicity, Customized Oriental	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants	2 participants n=8 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	1 participants n=21 Participants	10 participants n=8 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	2 participants n=8 Participants
Race/Ethnicity, Customized Thai	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	1 participants n=8 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	0 participants n=21 Participants	10 participants n=8 Participants
Baseline Severity (First Attack) Grades 0, 1: No pain, Mild, or Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=8 Participants
Baseline Severity (First Attack) Grade 2: Moderate	58 Participants n=5 Participants	66 Participants n=7 Participants	69 Participants n=5 Participants	46 Participants n=4 Participants	64 Participants n=21 Participants	303 Participants n=8 Participants
Baseline Severity (First Attack) Grade 3: Severe	24 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	29 Participants n=4 Participants	17 Participants n=21 Participants	100 Participants n=8 Participants

PRIMARY outcome

Timeframe: 2 hours

Population: The primary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase.

Outcome measures

Outcome measures
Measure	Rizatriptan 10 mg n=320 Participants All Rizatriptan 10 mg patients from all Treatment Sequences	Placebo n=82 Participants All Placebo patients from all Treatment Sequences
Pain Relief at 2 Hours During the First Migraine Attack Period Reporting pain relief	246 participants	30 participants
Pain Relief at 2 Hours During the First Migraine Attack Period Not reporting pain relief	74 participants	52 participants

SECONDARY outcome

Timeframe: 2 hours

Population: The secondary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase. Values were not carried forward from one attack period to the next.

Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the second migraine attack

Outcome measures

Outcome measures
Measure	Rizatriptan 10 mg n=291 Participants All Rizatriptan 10 mg patients from all Treatment Sequences	Placebo n=73 Participants All Placebo patients from all Treatment Sequences
Pain Relief at 2 Hours During the Second Migraine Attack Period Reporting pain relief	228 Participants	27 Participants
Pain Relief at 2 Hours During the Second Migraine Attack Period Not reporting pain relief	63 Participants	46 Participants

SECONDARY outcome

Timeframe: 2 hours

Outcome measures

Outcome measures
Measure	Rizatriptan 10 mg n=259 Participants All Rizatriptan 10 mg patients from all Treatment Sequences	Placebo n=75 Participants All Placebo patients from all Treatment Sequences
Pain Relief at 2 Hours During the Third Migraine Attack Period Reporting pain relief	207 Participants	21 Participants
Pain Relief at 2 Hours During the Third Migraine Attack Period Not reporting pain relief	52 Participants	54 Participants

SECONDARY outcome

Timeframe: 2 hours

Outcome measures

Outcome measures
Measure	Rizatriptan 10 mg n=255 Participants All Rizatriptan 10 mg patients from all Treatment Sequences	Placebo n=57 Participants All Placebo patients from all Treatment Sequences
Pain Relief at 2 Hours During the Fourth Migraine Attack Period Reporting pain relief	190 Participants	31 Participants
Pain Relief at 2 Hours During the Fourth Migraine Attack Period Not reporting pain relief	65 Participants	26 Participants

Adverse Events

Rizatriptan 10 mg

Serious events: 0 serious events

Other events: 199 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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 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

Other adverse events
Measure	Rizatriptan 10 mg n=323 participants at risk；n=337 participants at risk All Rizatriptan 10 mg patients from all Treatment Sequences	Placebo n=84 participants at risk All Placebo patients from all Treatment Sequences
General disorders Asthenia/Fatigue	5.3% 17/323 • 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% 0/84 • 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 Candidiasis	0.00% 0/323 • 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.	1.2% 1/84 • 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 Chills	0.00% 0/323 • 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.	1.2% 1/84 • 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 Fever	0.31% 1/323 • 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.	1.2% 1/84 • 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	1.5% 5/323 • 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% 0/84 • 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	3.4% 11/323 • 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.	1.2% 1/84 • 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.
Cardiac disorders Palpitation	1.2% 4/323 • 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% 0/84 • 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.
Cardiac disorders Tachycardia	1.2% 4/323 • 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% 0/84 • 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 Diarrhea	0.93% 3/323 • 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.	1.2% 1/84 • 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	3.4% 11/323 • 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.	1.2% 1/84 • 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	7.1% 23/323 • 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.	2.4% 2/84 • 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	1.5% 5/323 • 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.	1.2% 1/84 • 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.
Endocrine disorders Hypothyroidism	0.00% 0/323 • 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.	1.2% 1/84 • 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.
Blood and lymphatic system disorders Leukocytes Decreased	1.2% 4/323 • 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% 0/84 • 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	1.2% 4/323 • 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% 0/84 • 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 Abnormal Sensation	0.62% 2/323 • 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.	1.2% 1/84 • 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 Ataxia	0.00% 0/323 • 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.	1.2% 1/84 • 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	9.0% 29/323 • 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% 4/84 • 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.
Psychiatric disorders Euphoria	1.5% 5/323 • 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% 0/84 • 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	1.9% 6/323 • 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.	1.2% 1/84 • 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	0.62% 2/323 • 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.	1.2% 1/84 • 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 Mental Acuity Decreased	1.9% 6/323 • 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.	2.4% 2/84 • 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 Nervousness	0.31% 1/323 • 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.	1.2% 1/84 • 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	4.0% 13/323 • 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% 0/84 • 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	8.7% 28/323 • 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% 4/84 • 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 Dyspnea	1.2% 4/323 • 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% 0/84 • 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	0.62% 2/323 • 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.	2.4% 2/84 • 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	2.2% 7/323 • 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.	1.2% 1/84 • 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 Accommodation Disorder	0.00% 0/323 • 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.	1.2% 1/84 • 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.
Eye disorders Depth Perception Loss	0.00% 0/323 • 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.	1.2% 1/84 • 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	0.62% 2/323 • 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.	1.2% 1/84 • 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.