Trial Outcomes & Findings for Lubiprostone for Chronic Idiopathic Constipation Treatment (NCT NCT02729909)

Last Updated: 2019-04-01

Results Overview

A SBM is defined as any bowel movement (BM) that does not occur within 24 hours after rescue medication use (laxative, suppository, or enema). Participants were given a diary to complete at home where they have recorded all details of each SBM including the consistency of the stool and the difficulty they have in passing it.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

211 participants

Primary outcome timeframe

Week 1

Results posted on

2019-04-01

Participant Flow

Participants took part in the study at 10 investigative sites in Mexico from 11 May 2016 to 05 June 2017.

Participants with a diagnosis of chronic idiopathic constipation were enrolled in a 1:1 ratio in one of two treatment groups to receive either lubiprostone 24 µg or placebo.

Participant milestones

Participant milestones
Measure	Lubiprostone 24 μg Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Overall Study STARTED	105	106
Overall Study COMPLETED	104	101
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Lubiprostone 24 μg Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Overall Study Lost to Follow-up	0	1
Overall Study Lack of Efficacy	0	2
Overall Study Significant Protocol Deviation	0	2
Overall Study Voluntary Withdrawal	1	0

Baseline Characteristics

Lubiprostone for Chronic Idiopathic Constipation Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.	Total n=211 Participants Total of all reporting groups
Race/Ethnicity, Customized American Indian or Alaska Native	73 Participants n=5 Participants	67 Participants n=7 Participants	140 Participants n=5 Participants
Race/Ethnicity, Customized White	27 Participants n=5 Participants	30 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized Multiracial	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Mexico	105 Participants n=5 Participants	106 Participants n=7 Participants	211 Participants n=5 Participants
Height	161.9 cm STANDARD_DEVIATION 8.12 • n=5 Participants	160.7 cm STANDARD_DEVIATION 7.42 • n=7 Participants	161.3 cm STANDARD_DEVIATION 7.78 • n=5 Participants
Weight	72.48 kg STANDARD_DEVIATION 13.916 • n=5 Participants	70.67 kg STANDARD_DEVIATION 12.873 • n=7 Participants	71.57 kg STANDARD_DEVIATION 13.401 • n=5 Participants
Body Mass Index (BMI)	27.638 kg/m^2 STANDARD_DEVIATION 4.6950 • n=5 Participants	27.333 kg/m^2 STANDARD_DEVIATION 4.3830 • n=7 Participants	27.485 kg/m^2 STANDARD_DEVIATION 4.5326 • n=5 Participants
Smokers Participant had never smoked	78 Participants n=5 Participants	88 Participants n=7 Participants	166 Participants n=5 Participants
Smokers Participant was a current smoker	23 Participants n=5 Participants	13 Participants n=7 Participants	36 Participants n=5 Participants
Smokers Participant was an ex-smoker	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	43.3 years n=5 Participants	40.8 years n=7 Participants	42.05 years n=5 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	90 Participants n=7 Participants	172 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	16 Participants n=7 Participants	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 1

Population: Full Analysis Set (FAS) included all participants randomized to receive study treatment whether or not they received treatment. Missing values were imputed by using last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Spontaneous Bowel Movement (SBM) Frequency at Week 1 of Administration	6.7 number of SBM per week Standard Deviation 4.55	5.2 number of SBM per week Standard Deviation 2.82

SECONDARY outcome

Timeframe: Weeks 2, 3 and 4

Population: FAS included all participants randomized to receive study treatment whether or not they received treatment. Missing values were imputed by using LOCF.

A SBM is defined as any BM that does not occur within 24 hours after rescue medication use (laxative, suppository, or enema). Participants were given a diary to complete at home where they have recorded all details of each SBM including the consistency of the stool and the difficulty they have in passing it.

Outcome measures

Outcome measures
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
SBM Frequency at Weeks 2, 3 and 4 Week 2	6.9 number of SBM per week Standard Deviation 4.40	5.5 number of SBM per week Standard Deviation 2.75
SBM Frequency at Weeks 2, 3 and 4 Week 3	7.6 number of SBM per week Standard Deviation 4.50	6.0 number of SBM per week Standard Deviation 3.74
SBM Frequency at Weeks 2, 3 and 4 Week 4	7.2 number of SBM per week Standard Deviation 4.21	5.8 number of SBM per week Standard Deviation 3.39

SECONDARY outcome

Timeframe: Up to 24 hours after the first dose of study medication

Population: FAS included all participants randomized to receive study treatment whether or not they received treatment.

A SBM is defined as any BM that does not occur within 24 hours after rescue medication use. Percentage of participants who have an SBM within 24 hours after the first dose was assessed and derived from the data on SBMs collected in the participant diary.

Outcome measures

Outcome measures
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Percentage of Participants Who Have a SBM Within 24 Hours After First Dose of Study Medication	60.0 percentage of participants	41.5 percentage of participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 3 and 4

Population: FAS included all participants randomized to receive study treatment whether or not they received treatment. Missing values were imputed by using LOCF.

For each participant, the mean degree of straining was averaged for all SBMs in a given week. The degree of straining for each SBM was collected in the participant diary. The degree of straining was scored on a 5-point scale where: 0=No straining, 1=Mild straining, 2=Moderate straining, 3=Strong straining or 4=Very strong straining with higher scores indicating more severe straining.

Outcome measures

Outcome measures
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Mean Degree of Straining Score Week 1	1.6 score on a scale Standard Deviation 0.85	2.0 score on a scale Standard Deviation 0.88
Mean Degree of Straining Score Week 2	1.5 score on a scale Standard Deviation 0.89	1.8 score on a scale Standard Deviation 0.93
Mean Degree of Straining Score Week 3	1.3 score on a scale Standard Deviation 0.82	1.6 score on a scale Standard Deviation 0.92
Mean Degree of Straining Score Week 4	1.2 score on a scale Standard Deviation 0.92	1.5 score on a scale Standard Deviation 0.86

SECONDARY outcome

Timeframe: Weeks 1, 2, 3 and 4

Population: FAS included all participants randomized to receive study treatment whether or not they received treatment. Missing values were imputed by using LOCF.

For each participant, the mean stool consistency score was averaged for all SBMs in a given week. The mean degree of stool consistency for each SBM was collected in the participant diary based on the Bristol Stool Chart. The Bristol Stool Chart is a medical aid designed to classify the form of human feces into seven categories where: 1=Hard and round (difficult-to-pass), 2=Sausage-shaped but hard stool, 3=Sausage-shaped stool with cracks on the surface, 4=Sausage-shaped, soft stool with smooth surface, or coiled stool, 5=Soft, half-solid (and easy-to-pass) stool with clear crease, 6=Unshaped, loose stool with small, irregular-shaped pieces, or mushy stool or 7=Watery stool without solid pieces (entirely liquid).

Outcome measures

Outcome measures
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Mean Degree of Stool Consistency Week 1	4.1 score on a scale Standard Deviation 1.30	3.4 score on a scale Standard Deviation 1.08
Mean Degree of Stool Consistency Week 2	4.1 score on a scale Standard Deviation 1.13	3.5 score on a scale Standard Deviation 1.05
Mean Degree of Stool Consistency Week 3	4.1 score on a scale Standard Deviation 1.12	3.5 score on a scale Standard Deviation 0.93
Mean Degree of Stool Consistency Week 4	4.1 score on a scale Standard Deviation 1.19	3.6 score on a scale Standard Deviation 0.93

SECONDARY outcome

Timeframe: Weeks 1, 2, 3 and 4

Population: FAS included all participants randomized to receive study treatment whether or not they received treatment. Missing values were imputed by using LOCF.

Weekly abdominal symptoms of bloating and discomfort upon waking in the morning was scored weekly on a 5-point scale where: 0=None, 1=Mild, 2=Moderate, 3=Severe or 4=Very severe, with a higher score indicating more severe symptoms. Assessment of weekly abdominal symptoms were recorded in the participant in the diary.

Outcome measures

Outcome measures
Measure	Lubiprostone 24 μg n=105 Participants Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 Participants Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Weekly Abdominal Symptoms Score Week 3	1.0 score on a scale Standard Deviation 1.01	1.4 score on a scale Standard Deviation 0.93
Weekly Abdominal Symptoms Score Week 1	1.4 score on a scale Standard Deviation 1.05	1.8 score on a scale Standard Deviation 0.96
Weekly Abdominal Symptoms Score Week 2	1.2 score on a scale Standard Deviation 0.93	1.5 score on a scale Standard Deviation 1.01
Weekly Abdominal Symptoms Score Week 4	0.9 score on a scale Standard Deviation 0.94	1.2 score on a scale Standard Deviation 0.98

Adverse Events

Lubiprostone 24 μg

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

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

Measure	Lubiprostone 24 μg n=105 participants at risk Lubiprostone 24 μg, capsules, orally, twice daily, under fed conditions, for 4 weeks.	Placebo n=106 participants at risk Lubiprostone placebo-matching capsules, orally, twice daily, under fed conditions, for 4 weeks.
Blood and lymphatic system disorders Neutropenia	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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.
Endocrine disorders Hypothyroidism	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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 Diarrhoea	9.5% 10/105 • First dose of study drug up to Week 6 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.	1.9% 2/106 • First dose of study drug up to Week 6 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 Nausea	1.9% 2/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Abdominal pain	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Abdominal pain upper	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Dyspepsia	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Abdominal discomfort	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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 Haemorrhoids	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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 Peripheral swelling	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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 Influenza	2.9% 3/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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	2.9% 3/105 • First dose of study drug up to Week 6 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% 4/106 • First dose of study drug up to Week 6 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 Bronchitis	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Oral herpes	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Pharyngitis	0.95% 1/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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 Limb injury	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Lymphocyte count increased	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 bilirubin increased	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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	0.00% 0/105 • First dose of study drug up to Week 6 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.	1.9% 2/106 • First dose of study drug up to Week 6 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 thyroid stimulating hormone increased	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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 Arthralgia	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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 Back pain	0.00% 0/105 • First dose of study drug up to Week 6 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.	0.94% 1/106 • First dose of study drug up to Week 6 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	1.9% 2/105 • First dose of study drug up to Week 6 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.	2.8% 3/106 • First dose of study drug up to Week 6 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	0.95% 1/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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.
Reproductive system and breast disorders Dysmenorrhoea	1.9% 2/105 • First dose of study drug up to Week 6 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% 0/106 • First dose of study drug up to Week 6 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.