Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 25 and 50mg in Asia Pacific Adults With Type 2 Diabetes (NCT NCT01647542)

Last Updated: 2015-11-11

Results Overview

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to baseline.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

393 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2015-11-11

Participant Flow

Participants took part in the study at 59 investigative sites in Australia, China, the Republic of Korea, New Zealand and Taiwan from 30 July 2012 to 18 March 2014.

Participants with a historical diagnosis of type 2 diabetes mellitus (T2DM) who were inadequately controlled when treated with only diet, exercise and any antidiabetic agent for less than or equal to (\<=) 7 days within 12 weeks prior to Screening, were enrolled in 1 of 3 treatment groups: placebo; fasiglifam 25 milligram (mg); fasiglifam 50 mg.

Participant milestones

Participant milestones
Measure	Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.	Placebo Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.
Overall Study STARTED	131	131	131
Overall Study COMPLETED	58	59	55
Overall Study NOT COMPLETED	73	72	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.	Placebo Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.
Overall Study Major Protocol Deviation	0	0	1
Overall Study Adverse Event	5	4	4
Overall Study Lost to Follow-up	2	2	0
Overall Study Withdrawal by Subject	4	0	6
Overall Study Study Termination	61	65	64
Overall Study Lack of Efficacy	1	0	1
Overall Study Death	0	1	0

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 25 and 50mg in Asia Pacific Adults With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=131 Participants Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=131 Participants Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=131 Participants Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.	Total n=393 Participants Total of all reporting groups
Age, Continuous	52.7 years STANDARD_DEVIATION 12.41 • n=5 Participants	55.1 years STANDARD_DEVIATION 11.89 • n=7 Participants	53.1 years STANDARD_DEVIATION 10.96 • n=5 Participants	53.6 years STANDARD_DEVIATION 11.78 • n=4 Participants
Age, Customized Less than (<) 65 years	107 Participants n=5 Participants	102 Participants n=7 Participants	111 Participants n=5 Participants	320 Participants n=4 Participants
Age, Customized Greater than or equal to (>=) 65 years	24 Participants n=5 Participants	29 Participants n=7 Participants	20 Participants n=5 Participants	73 Participants n=4 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	61 Participants n=7 Participants	44 Participants n=5 Participants	169 Participants n=4 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	70 Participants n=7 Participants	87 Participants n=5 Participants	224 Participants n=4 Participants
Race/Ethnicity, Customized Asian	128 Participants n=5 Participants	126 Participants n=7 Participants	127 Participants n=5 Participants	381 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Body Mass Index	26.00 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.348 • n=5 Participants	25.97 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.989 • n=7 Participants	26.12 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.516 • n=5 Participants	26.03 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.956 • n=4 Participants
Smoking Classification Never smoked	89 Participants n=5 Participants	90 Participants n=7 Participants	71 Participants n=5 Participants	250 Participants n=4 Participants
Smoking Classification Current smoker	31 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants	80 Participants n=4 Participants
Smoking Classification Ex-smoker	11 Participants n=5 Participants	25 Participants n=7 Participants	27 Participants n=5 Participants	63 Participants n=4 Participants
Glycosylated Hemoglobin (HbA1c) Category < 8.5 percent (%)	98 Participants n=5 Participants	99 Participants n=7 Participants	107 Participants n=5 Participants	304 Participants n=4 Participants
Glycosylated Hemoglobin (HbA1c) Category >= 8.5%	33 Participants n=5 Participants	32 Participants n=7 Participants	24 Participants n=5 Participants	89 Participants n=4 Participants
Enrollment by Region Australia	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Enrollment by Region China	70 Participants n=5 Participants	70 Participants n=7 Participants	70 Participants n=5 Participants	210 Participants n=4 Participants
Enrollment by Region Korea, Republic of	26 Participants n=5 Participants	29 Participants n=7 Participants	28 Participants n=5 Participants	83 Participants n=4 Participants
Enrollment by Region New Zealand	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Enrollment by Region Taiwan, Province of China	28 Participants n=5 Participants	25 Participants n=7 Participants	26 Participants n=5 Participants	79 Participants n=4 Participants
Duration of Diabetes	2.293 Years STANDARD_DEVIATION 3.063 • n=5 Participants	3.499 Years STANDARD_DEVIATION 3.64 • n=7 Participants	2.182 Years STANDARD_DEVIATION 2.782 • n=5 Participants	2.652 Years STANDARD_DEVIATION 3.227 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set (FAS) included of all randomized participants who received at least 1 dose of double blind study medication. Only participants with a baseline and at least 1 post-baseline value were included.

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=120 Participants Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=124 Participants Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=131 Participants Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.
Change From Baseline in HbA1c at Week 24 Change at Week 24 (n= 52, 61, 59)	0.15 Percentage of Glycosylated Hemoglobin Standard Error 0.101	-0.67 Percentage of Glycosylated Hemoglobin Standard Error 0.097	-0.87 Percentage of Glycosylated Hemoglobin Standard Error 0.097
Change From Baseline in HbA1c at Week 24 Baseline (n= 120, 124, 131)	7.99 Percentage of Glycosylated Hemoglobin Standard Error 0.104	7.94 Percentage of Glycosylated Hemoglobin Standard Error 0.101	7.91 Percentage of Glycosylated Hemoglobin Standard Error 0.102

SECONDARY outcome

Timeframe: Week 24

Population: FAS included of all randomized participants who received at least 1 dose of double blind study medication. Only Participants with a baseline and at least 1 post baseline value were included.

Outcome measures

Outcome measures
Measure	Placebo n=120 Participants Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=124 Participants Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=131 Participants Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.
Percentage of Participants With HbA1c <7% at Week 24	20.0 Percentage of participants	42.7 Percentage of participants	52.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS included of all randomized participants who received at least 1 dose of double blind study medication. Only participants with a baseline and at least 1 post baseline value were included

The change between the fasting plasma glucose value collected at Week 24 relative to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=129 Participants Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=127 Participants Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=129 Participants Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.
Change in Fasting Plasma Glucose From Baseline to Week 24 Baseline (n =129, 127, 129)	152.4 Milligram per deciliter (mg/dL) Standard Error 4.74	152.4 Milligram per deciliter (mg/dL) Standard Error 4.67	149.7 Milligram per deciliter (mg/dL) Standard Error 4.74
Change in Fasting Plasma Glucose From Baseline to Week 24 Change at Week 24 (n = 51, 58, 57)	15.1 Milligram per deciliter (mg/dL) Standard Error 3.59	-20.6 Milligram per deciliter (mg/dL) Standard Error 3.42	-20.4 Milligram per deciliter (mg/dL) Standard Error 3.45

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS included of all randomized participants who received at least 1 dose of double blind study medication. Only participants with a baseline and at least 1 post-baseline value were included.

The change between the value of glucose after a meal, measured following OGTT collected at Week 24 relative to baseline. Oral glucose tolerance test measures glucose, insulin, and C-peptide through blood samples drawn at 0, 30, 60, 90, and 120 minutes following consumption of a 75 gram (g) glucose beverage.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=6 Participants Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=7 Participants Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following Oral Glucose Tolerance Test (OGTT) at Week 24 Baseline	150.3 mg/dL Standard Error 21.69	121.2 mg/dL Standard Error 22.76	129.0 mg/dL Standard Error 18.72
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following Oral Glucose Tolerance Test (OGTT) at Week 24 Change at Week 24	3.7 mg/dL Standard Error 24.58	-21.2 mg/dL Standard Error 25.98	9.6 mg/dL Standard Error 21.15

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 39 other events

Deaths: 0 deaths

Fasiglifam 25 mg

Serious events: 5 serious events

Other events: 51 other events

Deaths: 0 deaths

Fasiglifam 50 mg

Serious events: 8 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo n=131 participants at risk Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=131 participants at risk Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=131 participants at risk Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.
Cardiac disorders Hypertensive heart disease	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Acute coronary syndrome	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastritis erosive	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholecystitis	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hepatitis acute	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Gastroenteritis	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Epiglottitis	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Liver function test abnormal	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Ischaemic stroke	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events
Measure	Placebo n=131 participants at risk Fasiglifam placebo-matching tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 25 mg n=131 participants at risk Fasiglifam 25 mg, tablets, orally, once daily, for up to 24 weeks.	Fasiglifam 50 mg n=131 participants at risk Fasiglifam 50 mg, tablets, orally, once daily, for up to 24 weeks.
Blood and lymphatic system disorders Thrombocytopenia	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Chest pain	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	6.1% 8/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.6% 6/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.1% 8/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	3.8% 5/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.6% 10/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.6% 6/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperuricaemia	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	9.2% 12/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	3.8% 5/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.3% 7/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Proteinuria	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 5/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 5/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Dyslipidaemia	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.1% 4/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 5/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperlipidaemia	3.1% 4/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.6% 6/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatine phosphokinase increased	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 5/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.1% 4/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.1% 4/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hepatic function abnormal	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Insulin resistance	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.76% 1/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Palpitations	2.3% 3/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.5% 2/131 • Treatment -emergent adverse events are adverse events that started after the first dose of double- blind study drug and no more than 30 days after the last dose of double blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.