Trial Outcomes & Findings for MK0524B Bioequivalence Study (0524B-070) (NCT NCT00943124)

NCT ID: NCT00943124

Last Updated: 2015-06-19

Results Overview

Plasma Area Under the Curve of simvastatin acid, the active metabolite of simvastatin

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

220 participants

Primary outcome timeframe

Through 48 Hours Post Dose

Results posted on

2015-06-19

Participant Flow

Participant milestones

Participant milestones
Measure	MK0524B Then Simvastatin + MK0524A Period 1: 1 tablet of MK0524B (ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet). Period 2: 1 tablet of simvastatin and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets.	Simvastatin + MK0524A Then MK0524B Period 1: 1 tablet of simvastatin and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets. Period 2: 1 tablet of MK0524B (ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet).
Period 1 STARTED	110	110
Period 1 COMPLETED	108	108
Period 1 NOT COMPLETED	2	2
Period 2 STARTED	108	108
Period 2 COMPLETED	108	108
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	MK0524B Then Simvastatin + MK0524A Period 1: 1 tablet of MK0524B (ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet). Period 2: 1 tablet of simvastatin and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets.	Simvastatin + MK0524A Then MK0524B Period 1: 1 tablet of simvastatin and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets. Period 2: 1 tablet of MK0524B (ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet).
Period 1 Withdrawal by Subject	1	1
Period 1 Did Not Follow Study Procedures	1	0
Period 1 Personal Reasons	0	1

Baseline Characteristics

MK0524B Bioequivalence Study (0524B-070)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study Population n=220 Participants All randomized patients
Age, Continuous	35.11 years n=5 Participants
Sex: Female, Male Female	92 Participants n=5 Participants
Sex: Female, Male Male	128 Participants n=5 Participants
Height	169.58 Centimeters n=5 Participants
Weight	72.99 Kilograms n=5 Participants

PRIMARY outcome

Timeframe: Through 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=10) and the limitation of the assay (N=10), data from a total of 200 and 202 subjects were available for simvastatin acid AUC(0 to 48 hour) analysis for MK0524B and Simvastatin + MK0524A, respectively.

Plasma Area Under the Curve of simvastatin acid, the active metabolite of simvastatin

Outcome measures

Outcome measures
Measure	MK0524B n=200 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=202 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Plasma Area Under the Curve (AUC(0 to 48hr)) for Simvastatin Acid	9.19 ng/mL * Hour Standard Deviation 8.38	8.03 ng/mL * Hour Standard Deviation 7.78

PRIMARY outcome

Timeframe: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=10) and the limitation of the assay (N=10), data from a total of 201 and 202 subjects were available for simvastatin acid Cmax analysis for MK0524B and Simvastatin + MK0524A, respectively.

Peak Plasma Concentration (Cmax) for Simvastatin Acid, the active metabolite of simvastatin

Outcome measures

Outcome measures
Measure	MK0524B n=201 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=202 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Peak Plasma Concentration (Cmax) of Simvastatin Acid	1.016 ng/mL Standard Deviation 0.946	0.918 ng/mL Standard Deviation 0.906

PRIMARY outcome

Timeframe: Through 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=2) and the limitation of the assay (N=10), data from a total of 208 and 210 subjects were available for simvastatin AUC(0-48 hour) analysis for MK0524B and Simvastatin + MK0524A, respectively.

Plasma Area Under the Curve of simvastatin

Outcome measures

Outcome measures
Measure	MK0524B n=208 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=210 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Plasma Area Under the Curve (AUC(0 to 48 Hour)) for Simvastatin	15.03 ng/mL * Hour Standard Deviation 9.88	15.56 ng/mL * Hour Standard Deviation 9.11

PRIMARY outcome

Timeframe: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), mis-handling of plasma samples (N=2) and the limitation of the assay (N=10), data from a total of 209 and 210 subjects were available for simvastatin Cmax analysis for MK0524B and Simvastatin + MK0524A, respectively.

Outcome measures

Outcome measures
Measure	MK0524B n=209 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=210 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Peak Plasma Concentration (Cmax) of Simvastatin	5.81 ng/mL Standard Deviation 4.31	6.33 ng/mL Standard Deviation 4.64

PRIMARY outcome

Timeframe: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), data from a total of 217 and 216 subjects were available for laropiprant AUC(0 to infinity) analysis for MK0524B and Simvastatin + MK0524A, respectively

Plasma Area Under the Curve of Laropiprant

Outcome measures

Outcome measures
Measure	MK0524B n=217 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=216 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Plasma Area Under the Curve (AUC(0 to Infinity)) for Laropiprant	5486 nmol/L * hour Standard Deviation 2832	5405 nmol/L * hour Standard Deviation 2618

PRIMARY outcome

Timeframe: 48 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), data from a total of 217 and 216 subjects were available for laropiprant Cmax analysis for MK0524B and Simvastatin + MK0524A, respectively

Outcome measures

Outcome measures
Measure	MK0524B n=217 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=216 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Peak Plasma Concentration (Cmax) of Laropiprant	1030 nmol/L Standard Deviation 642	953 nmol/L Standard Deviation 542

PRIMARY outcome

Timeframe: 24 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4) and missing samples (N=1), data from a total of 215 and 216 subjects available for plasma nicotinuric acid analysis for MK0524B and Simvastatin + MK0524A, respectively.

Peak Plasma Concentration (Cmax) for Nicotinuric Acid, one of the active metabolites of Niacin

Outcome measures

Outcome measures
Measure	MK0524B n=215 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=216 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Peak Plasma Concentration (Cmax) of Nicotinuric Acid	620 ng/mL Standard Deviation 536	807 ng/mL Standard Deviation 469

PRIMARY outcome

Timeframe: 96 Hours Post Dose

Population: Two hundred-twenty (220) subjects were enrolled in this study. Due to early dropout (N=4), data from a total of 216 subjects were available for both MK0524B and Simvastatin + MK0524A for analysis of urinary excretion of nicotinuric acid and metabolites

Outcome measures

Outcome measures
Measure	MK0524B n=216 Participants MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=216 Participants Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Total Urinary Excretion of Niacin and Its Metabolites	5339 µmol Standard Deviation 968	5825 µmol Standard Deviation 1188

Adverse Events

MK0524B

Serious events: 0 serious events

Other events: 61 other events

Deaths: 0 deaths

Simvastatin + MK0524A

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Other adverse events
Measure	MK0524B n=220 participants at risk MK0524B: 1 tablet of ER Niacin 900 mg/laropiprant 20 mg/simvastatin 20 mg fixed dose combination tablet.	Simvastatin + MK0524A n=220 participants at risk Simvastatin + MK0524A : 1 tablet of simvastatin 20 mg (ZOCOR) and 1 tablet of MK0524A (ER Niacin 1000 mg/laropiprant 20 mg) as separate tablets
Cardiac disorders Palpitations	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Ear and labyrinth disorders Ear Discomfort	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Eye disorders Ocular Hyperaemia	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Abdominal Pain	3.2% 7/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Abdominal Pain Upper	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Aphthous Stomatitis	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Chapped Lips	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Constipation	2.7% 6/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Diarrhoea	1.8% 4/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Dry Mouth	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Dyspepsia	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Eructation	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Nausea	6.8% 15/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	5.5% 12/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Salivary Hypersecretion	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Toothache	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Gastrointestinal disorders Vomiting	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	2.3% 5/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
General disorders Fatigue	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
General disorders Feeling Hot	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
General disorders Feeling Jittery	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
General disorders Malaise	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
General disorders Pain	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Infections and infestations Tooth Infection	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Injury, poisoning and procedural complications Arthropod Bite	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Injury, poisoning and procedural complications Contusion	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Injury, poisoning and procedural complications Wound	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Metabolism and nutrition disorders Anorexia	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Musculoskeletal and connective tissue disorders Back Pain	1.8% 4/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Musculoskeletal and connective tissue disorders Pain In Extremity	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Burning Sensation	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Dizziness	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Dysgeusia	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Headache	4.1% 9/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	7.7% 17/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Migraine	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Paraesthesia	1.8% 4/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	1.4% 3/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Somnolence	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Syncope	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Nervous system disorders Syncope Vasovagal	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.91% 2/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Psychiatric disorders Hypervigilance	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.
Psychiatric disorders Restlessness	0.45% 1/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.	0.00% 0/220 Although a subject/patient may have had two or more clinical adverse experiences, the subject/patient is counted only once within a category. The same subject/patient may appear in different categories.