Trial Outcomes & Findings for Rizatriptan 5 mg and 10 mg, Sumatriptan 100 mg, and Placebo Comparison Study (0462-030) (NCT NCT00898677)

NCT ID: NCT00898677

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 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: 1268 participants
• Primary outcome timeframe: 2 hours after dose
• Results posted on: 2022-02-03

Participant Flow

Patients were recruited at 47 sites in 21 countries in Canada, South America, Europe, Middle East, South Africa, and Australia First Patient Treated: September 1995 Last Patient Treated: May 1996

Outpatients screened at a pretreatment visit were given allocated drug supply with 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	Sumatriptan 100 mg Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Overall Study STARTED	180	455	455	178
Overall Study Patients Treated	164	387	388	160
Overall Study COMPLETED	163	386	383	159
Overall Study NOT COMPLETED	17	69	72	19

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	Sumatriptan 100 mg Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Overall Study Adverse Event	0	0	1	0
Overall Study Lost to Follow-up	0	0	2	0
Overall Study Protocol Violation	1	1	2	0
Overall Study Withdrawal by Subject	0	0	0	1
Overall Study Not Treated: Adverse Event	0	2	1	0
Overall Study Not Treated: Lost to Follow-Up	0	5	5	2
Overall Study Not Treated: Pregnancy	0	0	1	0
Overall Study Not Treated: Protocol Violation	2	0	2	0
Overall Study Not Treated: Withdraw by Subject	2	16	11	3
Overall Study Not Treated: Patient uncooperative	2	3	1	0
Overall Study Not Treated: Abnormal Prestudy Labs	0	0	0	1
Overall Study Not Treated: Abnormal Baseline ECG	1	0	0	0
Overall Study Not Treated: No Longer Met Inc Criteria	0	3	1	0
Overall Study Not Treated: Lack of Migraine Attack	9	39	43	12
Overall Study Not Treated: Other (Not Specified)	0	0	2	0

Baseline Characteristics

Rizatriptan 5 mg and 10 mg, Sumatriptan 100 mg, and Placebo Comparison Study (0462-030)

Baseline characteristics by cohort

Measure	Rizatriptan 5 mg n=164 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack. Baseline measure Participants reported are those participants that recieved study treatment.	Rizatriptan 10 mg n=387 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack Baseline measure Participants reported are those participants that recieved study treatment.	Sumatriptan 100 mg n=388 Participants Sumatriptan 100 mg orally once for treatment of single migraine attack Baseline measure Participants reported are those participants that recieved study treatment.	Placebo n=160 Participants Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack Baseline measure Participants reported are those participants that recieved study treatment.	Total n=1099 Participants Total of all reporting groups
Age, Continuous	38.3 years STANDARD_DEVIATION 10.3 • n=5 Participants	37.0 years STANDARD_DEVIATION 10.0 • n=7 Participants	39.2 years STANDARD_DEVIATION 10.1 • n=5 Participants	38.3 years STANDARD_DEVIATION 10.3 • n=4 Participants	38.2 years STANDARD_DEVIATION 10.2 • n=21 Participants
Sex: Female, Male Female	138 Participants n=5 Participants	319 Participants n=7 Participants	309 Participants n=5 Participants	132 Participants n=4 Participants	898 Participants n=21 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	68 Participants n=7 Participants	79 Participants n=5 Participants	28 Participants n=4 Participants	201 Participants n=21 Participants
Baseline Headache Severity Grades 1, 0: Mild, no pain, or missing	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Baseline Headache Severity Grade 2: Moderate	72 participants n=5 Participants	174 participants n=7 Participants	191 participants n=5 Participants	75 participants n=4 Participants	512 participants n=21 Participants
Baseline Headache Severity Grade 3: Severe	92 participants n=5 Participants	213 participants n=7 Participants	196 participants n=5 Participants	84 participants n=4 Participants	585 participants n=21 Participants
Race/Ethnicity Caucasian	117 participants n=5 Participants	282 participants n=7 Participants	281 participants n=5 Participants	120 participants n=4 Participants	800 participants n=21 Participants
Race/Ethnicity Black	1 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants	9 participants n=21 Participants
Race/Ethnicity Asian	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Race/Ethnicity Hispanic	33 participants n=5 Participants	80 participants n=7 Participants	77 participants n=5 Participants	32 participants n=4 Participants	222 participants n=21 Participants
Race/Ethnicity Mestizo	9 participants n=5 Participants	15 participants n=7 Participants	22 participants n=5 Participants	7 participants n=4 Participants	53 participants n=21 Participants
Race/Ethnicity Mexican	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	4 participants n=21 Participants
Race/Ethnicity Colored	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity Mexican/Hispanic	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity Mixed	2 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	5 participants n=21 Participants
Race/Ethnicity Asian/Caucasian	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: 2 hours after dose

Population: An "all-patients-treated" approach was used in the primary analysis, including all patients who had at least one assessment of pain severity within 2 hours after test medication. Missing values in the treatment phase (i.e., after the baseline phase) were imputed by carrying forward the preceding values in the same phase.

Patients 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

Outcome measures

Measure	Rizatriptan 5 mg n=164 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=385 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=387 Participants Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=159 Participants Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Pain Relief at 2 Hours After Dose 2-hour pain relief	99 Participants	258 Participants	239 Participants	64 Participants
Pain Relief at 2 Hours After Dose No 2-hour pain relief	65 Participants	127 Participants	148 Participants	95 Participants

PRIMARY outcome

Timeframe: within 2 hours after dose

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

Patients reporting time to relief defined as the first time point at which a patient reported headache severity grade 1 or 0 (mild pain or no headache) within 2 hours after dose

Outcome measures

Measure	Rizatriptan 5 mg n=164 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=385 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=387 Participants Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=159 Participants Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Time to Relief Within 2 Hours After Dose First pain relief within 2 hrs	102 Participants	265 Participants	247 Participants	72 Participants
Time to Relief Within 2 Hours After Dose Pain relief did not occur within 2 hrs	62 Participants	120 Participants	140 Participants	87 Participants

SECONDARY outcome

Timeframe: 2 hours after dose

Population: An "all-patients-treated" approach was used in the secondary analysis, including all patients who had at least one assessment of pain severity within 2 hours after test medication. Missing values in the treatment phase (i.e., after the baseline phase) were imputed by carrying forward the preceding values in the same phase.

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

Outcome measures

Measure	Rizatriptan 5 mg n=164 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=385 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=387 Participants Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=159 Participants Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Pain Free at 2 Hours After Dose 2-hour Pain freedom	41 Participants	155 Participants	127 Participants	15 Participants
Pain Free at 2 Hours After Dose No 2-hour pain freedom	123 Participants	230 Participants	260 Participants	139 Participants

SECONDARY outcome

Timeframe: 2 hours after dose

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

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

Outcome measures

Measure	Rizatriptan 5 mg n=164 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=385 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=387 Participants Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=159 Participants Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Functional Status at 2 Hours After Dose Required bed rest	23 Participants	42 Participants	52 Participants	36 Participants
Functional Status at 2 Hours After Dose No functional disability	52 Participants	160 Participants	126 Participants	31 Participants
Functional Status at 2 Hours After Dose Mildly impaired	62 Participants	123 Participants	142 Participants	59 Participants
Functional Status at 2 Hours After Dose Severely impaired	27 Participants	60 Participants	67 Participants	33 Participants

SECONDARY outcome

Timeframe: 2 hours after dose

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

Patients who recorded the presence or absence of nausea 2 hours after dose

Outcome measures

Measure	Rizatriptan 5 mg n=164 Participants Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=385 Participants Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=387 Participants Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=159 Participants Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Nausea at 2 Hours After Dose 2-hour Nausea	37 participants	95 participants	128 participants	68 participants
Nausea at 2 Hours After Dose No 2-hour Nausea	127 participants	290 participants	259 participants	91 participants

Adverse Events

Rizatriptan 5 mg

Serious events: 1 serious events

Other events: 62 other events

Deaths: 0 deaths

Rizatriptan 10 mg

Serious events: 0 serious events

Other events: 159 other events

Deaths: 0 deaths

Sumatriptan 100 mg

Serious events: 0 serious events

Other events: 188 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rizatriptan 5 mg n=164 participants at risk Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=387 participants at risk Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=388 participants at risk Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=160 participants at risk Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Reproductive system and breast disorders Endometriosis	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.

Other adverse events

Measure	Rizatriptan 5 mg n=164 participants at risk Rizatriptan 5 mg orally once for treatment of single migraine attack	Rizatriptan 10 mg n=387 participants at risk Rizatriptan 10 mg orally once for treatment of single migraine attack	Sumatriptan 100 mg n=388 participants at risk Sumatriptan 100 mg orally once for treatment of single migraine attack	Placebo n=160 participants at risk Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
General disorders Asthenia/Fatigue	2.4% 4/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	7.8% 30/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	8.2% 32/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.8% 6/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
General disorders Chills	1.8% 3/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.78% 3/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.5% 6/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
General disorders Cold Sensation	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.5% 4/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
General disorders Fever	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
General disorders Pain, Abdominal	4.3% 7/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.1% 12/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	5.2% 20/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
General disorders Pain, Chest	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.4% 13/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	5.7% 22/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.5% 4/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
General disorders Warm Sensation	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Cardiac disorders Palpitation	4.3% 7/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.6% 6/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Cardiac disorders Tachycardia	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.78% 3/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.8% 7/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Acid Regurgitation	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Diarrhea	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.3% 5/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.77% 3/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Dry Mouth	2.4% 4/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.3% 9/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.8% 7/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Dyspepsia	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.5% 6/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Nausea	4.9% 8/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	5.7% 22/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	9.0% 35/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.5% 4/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Vomiting	3.0% 5/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.1% 12/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.6% 10/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	5.0% 8/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Metabolism and nutrition disorders Alkaline Phosphatase Increased	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Metabolism and nutrition disorders Alanine Aminotransferase Increased	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.77% 3/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Metabolism and nutrition disorders Aspartate Aminotransferase Increased	1.8% 3/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.3% 5/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Metabolism and nutrition disorders Hypokalemia	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Musculoskeletal and connective tissue disorders Heaviness, Regional	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.6% 10/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.3% 9/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.3% 5/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Musculoskeletal and connective tissue disorders Pain, Neck	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Musculoskeletal and connective tissue disorders Pain, Shoulder	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Musculoskeletal and connective tissue disorders Stiffness	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Psychiatric disorders Anxiety	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.3% 9/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Psychiatric disorders Depression	1.8% 3/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.77% 3/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Nervous system disorders Dizziness	5.5% 9/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	7.8% 30/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	9.0% 35/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.8% 6/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Nervous system disorders Headache	1.8% 3/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.1% 12/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.8% 11/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Nervous system disorders Hypesthesia	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.3% 9/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Psychiatric disorders Insomnia	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.5% 6/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Psychiatric disorders Nervousness	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Nervous system disorders Paresthesia	1.8% 3/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.8% 11/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	4.1% 16/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	3.1% 5/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Psychiatric disorders Somnolence	7.9% 13/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	8.3% 32/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	7.2% 28/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	5.6% 9/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Nervous system disorders Tremor	2.4% 4/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.1% 8/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Respiratory, thoracic and mediastinal disorders Discomfort, Pharyngeal	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.8% 11/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.2% 2/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Skin and subcutaneous tissue disorders Flushing	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.52% 2/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Skin and subcutaneous tissue disorders Sweating	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.3% 5/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.6% 10/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.62% 1/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Eye disorders Blurred Vision	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.78% 3/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.3% 5/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Gastrointestinal disorders Perversion, Taste	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Reproductive system and breast disorders Hot Flashes	0.61% 1/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.0% 4/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	2.1% 8/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.
Renal and urinary disorders Urinary Frequency	0.00% 0/164 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.00% 0/387 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	0.26% 1/388 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.	1.2% 2/160 • 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. Adverse Event participants reported are those participants that received study treatment and had safety follow-up.

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