Trial Outcomes & Findings for MK0462 5 mg, Sumatriptan 50 mg, and Placebo Comparison Study (0462-029) (NCT NCT00897104)

Last Updated: 2022-02-03

Results Overview

Participants reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe pain) at baseline to grades 0 or 1 (no headache or mild pain) at 2 hours after treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

933 participants

Primary outcome timeframe

2 hours after treatment

Results posted on

2022-02-03

Participant Flow

Participants were recruited at 31 sites: 6 in UK, 9 in Norway, 2 in Switzerland, and 14 in Sweden First Participant Treated: August 1995 Last Participant Treated: May 1996.

Participants screened at a pretreatment visit were given allocated drug supply with instructions. If participants 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 participants still had not treated an attack, they were discontinued from the study.

Participant milestones

Participant milestones
Measure	Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Overall Study STARTED	418	428	87
Overall Study Participants Treated	355	357	80
Overall Study Participants Not Treated	63	71	7
Overall Study COMPLETED	354	357	79
Overall Study NOT COMPLETED	64	71	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Overall Study Lost to Follow-up	12	17	2
Overall Study Pregnancy	0	1	0
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	0	0	1
Overall Study Abnormal Prestudy Labs	2	0	0
Overall Study Abnormal Baseline ECG	2	2	0
Overall Study Need for Concom. Med.	0	1	1
Overall Study Lack of Migraine Attack	20	22	1
Overall Study No Longer Met Inc/Exc Criteria	1	0	0
Overall Study Other	3	0	0

Baseline Characteristics

MK0462 5 mg, Sumatriptan 50 mg, and Placebo Comparison Study (0462-029)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rizatriptan 5 mg n=355 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=357 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack	Total n=792 Participants Total of all reporting groups
Age, Continuous	39.9 years STANDARD_DEVIATION 10.3 • n=5 Participants	41.8 years STANDARD_DEVIATION 10.1 • n=7 Participants	44.3 years STANDARD_DEVIATION 10.5 • n=5 Participants	41.2 years STANDARD_DEVIATION 10.3 • n=4 Participants
Sex: Female, Male Female	291 Participants n=5 Participants	291 Participants n=7 Participants	70 Participants n=5 Participants	652 Participants n=4 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	66 Participants n=7 Participants	10 Participants n=5 Participants	140 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	352 participants n=5 Participants	356 participants n=7 Participants	80 participants n=5 Participants	788 participants n=4 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Baseline Headache Severity Grades 0,1: no pain, Mild, or missing	6 Participants n=5 Participants	8 Participants n=7 Participants	0 Participants n=5 Participants	14 Participants n=4 Participants
Baseline Headache Severity Grade 2: Moderate	216 Participants n=5 Participants	221 Participants n=7 Participants	51 Participants n=5 Participants	488 Participants n=4 Participants
Baseline Headache Severity Grade 3: Severe	133 Participants n=5 Participants	128 Participants n=7 Participants	29 Participants n=5 Participants	290 Participants n=4 Participants

PRIMARY outcome

Timeframe: 2 hours after treatment

Population: An "all-participants-treated" approach was used in the primary analysis, including all participants who had at least one assessment of pain severity within 2 hours after dose. Missing data were replaced by carrying forward the preceding value.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=352 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=356 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Pain Relief at 2 Hours After Treatment 2-hour pain relief	223 Participants	238 Participants	18 Participants
Pain Relief at 2 Hours After Treatment No 2-hour pain relief	129 Participants	118 Participants	62 Participants

PRIMARY outcome

Timeframe: within 2 hours after treatment

Population: An "all-participants-treated" approach was used in the primary analysis, including all participants who had at least one assessment of pain severity within 2 hours after test medication.

Participants reporting time to relief (defined as the first time that a participant reported grade 0 or 1 in headache severity within 2 hours after treatment (for the comparison of rizatriptan 5 mg and sumatriptan 50 mg).

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=352 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=356 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Time to Relief Within 2 Hours After Treatment First pain relief within 2 hrs	231 Participants	247 Participants	24 Participants
Time to Relief Within 2 Hours After Treatment Pain relief did not occur within 2 hrs	121 Participants	109 Participants	56 Participants

SECONDARY outcome

Timeframe: 2 hours after treatment

Population: An "all-participants-treated" approach was used in the secondary analysis, including all participants who had at least one assessment of pain severity within 2 hours after test medication. Missing data were replaced by carrying forward the preceding value.

Participants pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after treatment. Each participant rated headache severity on a 4-grade scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain).

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=352 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=356 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Pain Free at 2 Hours After Treatment 2-hour pain freedom	95 Participants	113 Participants	2 Participants
Pain Free at 2 Hours After Treatment No 2-hour pain freedom	257 Participants	243 Participants	78 Participants

SECONDARY outcome

Timeframe: 2 hours after treatment

Population: An "all-participants-treated" approach was used in the secondary analysis. Missing data were replaced by carrying forward the preceding value.

Participants with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each participant rated functional disability on a 4-grade scale (0 =normal; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 =unable to carry out daily activities, required bed rest).

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=350 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=355 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities Normal	108 Participants	116 Participants	4 Participants
Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities Mildly Impaired	152 Participants	148 Participants	28 Participants
Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities Severely Impaired	38 Participants	42 Participants	18 Participants
Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities Required Bed Rest	52 Participants	49 Participants	30 Participants

SECONDARY outcome

Timeframe: 2 hours after treatment

Population: "All-participants-treated" approach was used. Missing data were replaced by carrying forward the preceding value. Participants Analyzed For Nausea: Rizatriptan 348; Sumatriptan 352; Placebo 78. Participants Analyzed for Vomiting: Rizatriptan 342; Sumatriptan 342; Placebo 73. Number of participants analyzed is correct for the other categories.

Participants who recorded the presence or absence of the associated symptoms photophobia, phonophobia, nausea, and vomiting at 2 hours after treatment.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=350 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=354 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment 2-hour Nausea	105 Participants	131 Participants	48 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment No 2-hour Nausea	243 Participants	221 Participants	30 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment Not Analyzed for Nausea	2 Participants	2 Participants	2 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment 2-hour Vomiting	12 Participants	12 Participants	6 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment No 2-hour Vomiting	330 Participants	330 Participants	67 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment Not Analyzed for Vomiting	8 Participants	12 Participants	7 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment 2-hour Photophobia	161 Participants	153 Participants	66 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment No 2-hour Photophobia	189 Participants	201 Participants	14 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment 2-hour Phonophobia	126 Participants	125 Participants	47 Participants
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment No 2-hour Phonophobia	224 Participants	229 Participants	33 Participants

SECONDARY outcome

Timeframe: 2 hours after treatment

Population: An "all-participants-treated" approach was used in the secondary analysis. Missing data were replaced by carrying forward the preceding value.

Escape medication is defined as rescue medication for participants who experienced lack of efficacy from the study medication.

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=355 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=357 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Participants Who Used Escape Medication 2 Hours After the Treatment Dose Used Escape Medication	73 Participants	55 Participants	33 Participants
Participants Who Used Escape Medication 2 Hours After the Treatment Dose Did not Use Escape Medication	282 Participants	302 Participants	47 Participants

SECONDARY outcome

Timeframe: 24 hours

Population: The duration of relief, or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1), was calculated for responders who had a headache recurrence.

Duration of relief or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1) was calculated for responders who had a headache recurrence

Outcome measures

Outcome measures
Measure	Rizatriptan 5 mg n=84 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=80 Participants Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=6 Participants Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1])	11.07 Hours Standard Deviation 6.56	11.58 Hours Standard Deviation 5.86	14.38 Hours Standard Deviation 5.00

Adverse Events

Rizatriptan 5 mg

Serious events: 0 serious events

Other events: 92 other events

Deaths: 0 deaths

Sumatriptan 5 mg

Serious events: 0 serious events

Other events: 108 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 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

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 5 mg n=355 participants at risk Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg n=357 participants at risk Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo n=80 participants at risk Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
General disorders Asthenia/Fatigue	7.0% 25/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	5.0% 18/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
General disorders Fever	0.28% 1/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.28% 1/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
General disorders Pain, Abdominal	1.1% 4/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.4% 5/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
General disorders Pain, Chest	2.3% 8/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	4.5% 16/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
General disorders Warm Sensation	1.1% 4/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.84% 3/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Cardiac disorders Palpitation	0.56% 2/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.7% 6/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Cardiac disorders Tachycardia	0.56% 2/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.56% 2/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Gastrointestinal disorders Dry Mouth	2.8% 10/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	2.5% 9/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Gastrointestinal disorders Dyspepsia	0.28% 1/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.28% 1/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	2.5% 2/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Gastrointestinal disorders Nausea	3.7% 13/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	5.9% 21/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	2.5% 2/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Gastrointestinal disorders Pain, Mouth	0.00% 0/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Gastrointestinal disorders Vomiting	0.56% 2/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.4% 5/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Musculoskeletal and connective tissue disorders Heaviness, Regional	0.85% 3/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.1% 4/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Musculoskeletal and connective tissue disorders Pain, Back	0.00% 0/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.1% 4/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Musculoskeletal and connective tissue disorders Pain, Neck	0.56% 2/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	2.0% 7/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	2.5% 2/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Musculoskeletal and connective tissue disorders Stiffness	0.28% 1/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.4% 5/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Musculoskeletal and connective tissue disorders Strain	0.00% 0/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Psychiatric disorders Apathy	0.28% 1/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.28% 1/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Nervous system disorders Dizziness	3.7% 13/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	4.8% 17/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	5.0% 4/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Psychiatric disorders Dream Abnormality	0.00% 0/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.56% 2/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Nervous system disorders Headache	2.0% 7/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.7% 6/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Nervous system disorders Hypesthesia	1.1% 4/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.7% 6/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	3.8% 3/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Nervous system disorders Mental Acuity Decreased	0.85% 3/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.4% 5/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Nervous system disorders Paresthesia	3.1% 11/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	3.4% 12/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	2.5% 2/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Psychiatric disorders Somnolence	3.7% 13/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	4.8% 17/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Nervous system disorders Vertigo	1.7% 6/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.84% 3/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Respiratory, thoracic and mediastinal disorders Discomfort, Pharyngeal	1.4% 5/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.4% 5/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.00% 0/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/355 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	0.56% 2/357 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.	1.2% 1/80 • During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy. Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.