Trial Outcomes & Findings for Scopolamine in Bipolar Depression (NCT NCT04211961)

NCT ID: NCT04211961

Last Updated: 2025-04-29

Results Overview

Severity of objective depressive symptoms after the final scheduled treatment (Visit 6) as measured by the Hamilton Depression Rating Scale score. Possible scale range is 0-54, with higher values indicating greater severity of Depression.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

Approximately 2 weeks after randomisation (Visit 6)

Results posted on

2025-04-29

Participant Flow

Of the 55 participants who consented, 5 were withdrawn pre-randomisation. Three participants were deemed to have HDRS scores below the acceptable eligibility range (\<14). A single participant was withdrawn by PI due to being medically (physically) unfit to continue. A single participant withdrew consent due to difficulties with cannulation. Fifty participants were randomised into the SCOPE-BD trial.

Participant milestones

Participant milestones
Measure	Placebo Participants randomised to the placebo group will receive one 15-minute IV infusion of 100mL Saline at 4 visits.	Scopolamine Participants randomised to the treatment group will receive one 15-minute IV infusion of Scopolamine (dose 4μg/kg) at 4 visits.
Overall Study STARTED	24	26
Overall Study COMPLETED	24	23
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants randomised to the placebo group will receive one 15-minute IV infusion of 100mL Saline at 4 visits.	Scopolamine Participants randomised to the treatment group will receive one 15-minute IV infusion of Scopolamine (dose 4μg/kg) at 4 visits.
Overall Study Death	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Scopolamine in Bipolar Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=24 Participants The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=26 Participants The treatment group will receive a 100ml infusion of Scopolamine (dose 4μg/kg) at 4 visits during the study	Total n=50 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	42 years n=7 Participants	48 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	15 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Occupational status Employed full-time for pay	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Occupational status Employed part-time for pay	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Occupational status Full-time student	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Occupational status Homemaker	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Occupational status Leave of absence for medical reasons (plan to return to work)	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Occupational status Retired	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Occupational status Unemployed <6 months, but expects to work	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Occupational status Unemployed <6months, does not expect to work	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Occupational status Unemployed >=6months, but expects to work	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Occupational status Unemployed >=6months, does not expect to work	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Educational status College graduate	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Educational status Graduate professional training (Masters or above)	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Educational status High school graduate	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Educational status Junior hhigh school (7th,8th,9th)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Educational status Some college or technical school (at least one year)	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Educational status Some high school (10th,11th)	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Relationship status Divorced	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Relationship status Long-term relationship	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Relationship status Married	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Relationship status Single	10 Participants n=5 Participants	17 Participants n=7 Participants	27 Participants n=5 Participants
Socioeconomical status Machine operators, semiskilled workers	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Socioeconomical status Major business and professional	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Socioeconomical status Medium business, minor professional, technical	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Socioeconomical status Skilled craftsmen, clerical, sales workers	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Socioeconomical status Unskilled labourers, menial service workers	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Handedness Right-handed	20 Participants n=5 Participants	23 Participants n=7 Participants	43 Participants n=5 Participants
Handedness Left-handed	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Handedness Ambidextrous	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Psychosis	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Rapid cycling	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
History of involuntary hospitalisation for Bipolar episode	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
History of voluntary hospitalisation for Bipolar episode	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Smoker	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Substance use	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Alcohol use	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Alcohol dependence	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Cannabis use	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 2 weeks after randomisation (Visit 6)

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=24 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Hamilton Depression Rating Scale Score After Last Treatment	12.0 units on a scale Interval 7.0 to 15.5	13.0 units on a scale Interval 10.8 to 17.0

SECONDARY outcome

Timeframe: Approximately 2 weeks after randomisation (Visit 6)

Remission of depressive episode after the last IV treatment (measured objectively at Visit 6), defined as occurring when an individual has a Hamilton Depression Rating Scale score \<= 7 and a Montgomery and Asberg Depression Scale (MADRS) score \<6. The Hamilton Depression Rating Scale possible scale range is 0-54, with higher values indicating greater severity of Depression. The Montgomery-Åsberg Depression Rating Scale Score possible range is 0-60 with higher scores indicating greater severity of Depression.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=24 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Remission of Depressive Episode After Last Treatment (Visit 6)	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Approximately 4 weeks after randomisation (visit 7)

Remission of depressive episode at followup (measured objectively at Visit 7), defined as occurring when an individual has a Hamilton Depression Rating Scale score \<= 7 and a Montgomery and Asberg Depression Scale (MADRS) score \<6. he Hamilton Depression Rating Scale possible scale range is 0-54, with higher values indicating greater severity of Depression. The Montgomery-Åsberg Depression Rating Scale Score possible range is 0-60 with higher scores indicating greater severity of Depression.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=23 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Remission of Depressive Episode at Followup (Visit 7)	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Approximately 2 weeks after randomisation (visit 6)

Response to a depressive episode after the last IV treatment (measured at Visit 6) defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale score at Visit 6 compared to Visit 3. The Montgomery-Åsberg Depression Rating Scale Score possible range is 0-60 with higher scores indicating greater severity of Depression.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=24 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Response to a Depressive Episode After the Last IV Treatment (Visit 6)	9 Participants	7 Participants

SECONDARY outcome

Timeframe: At the time of followup at Visit 7, about 4 weeks after randomisation

Response at Visit 7, defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale score at Visit 7 compared to Visit 3.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=23 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Remission of Depressive Episode at Followup	7 Participants	6 Participants

SECONDARY outcome

Timeframe: After last treatment (Visit 6), about 2 weeks after randomisation

Montgomery-Åsberg Depression Rating Scale Score After Last Treatment (Visit 6). The The Montgomery-Åsberg Depression Rating Scale Score possible range is 0-60 with higher scores indicating greater severity of Depression.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=24 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Montgomery-Åsberg Depression Rating Scale Score After Last Treatment (Visit 6)	14 units on a scale Interval 9.0 to 20.0	16 units on a scale Interval 10.0 to 27.0

SECONDARY outcome

Timeframe: After last treatment (Visit 6), about 2 weeks after randomisation

POMS profile of mood scale is a questionnaire containing 65 words/statements that describe feelings people have. Total Score has range from 0-200 with higher scores indicating greater mood disturbance.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=23 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Total Profile of Mood States Score After Last Treatment (Visit 6)	27 units on a scale Interval 9.0 to 51.0	41 units on a scale Interval 16.0 to 93.0

SECONDARY outcome

Timeframe: At the time of followup (Visit 7), about 4 weeks after randomisation

Severity of objective depressive symptoms at followup (Visit 7) as measured by the Hamilton Depression Rating Scale score. Possible scale range is 0-54, with higher values indicating greater severity of Depression.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=23 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Hamilton Depression Rating Scale Score at Followup	9 units on a scale Interval 5.0 to 14.0	12 units on a scale Interval 10.0 to 15.0

SECONDARY outcome

Timeframe: At the time of followup (Visit 7), about 4 weeks after randomisation

Montgomery-Åsberg Depression Rating Scale Score at followup (Visit 7). The Montgomery-Åsberg Depression Rating Scale Score possible range is 0-60 with higher scores indicating greater severity of Depression.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=23 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Montgomery-Åsberg Depression Rating Scale Score at Followup	14 units on a scale Interval 9.0 to 20.0	16 units on a scale Interval 10.0 to 27.0

SECONDARY outcome

Timeframe: At the time of followup (Visit 7), about 4 weeks after randomisation

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=23 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Total Profile of Mood States Score at Followup (Visit 7)	19 units on a scale Interval 2.0 to 65.0	61 units on a scale Interval 30.0 to 84.0

SECONDARY outcome

Timeframe: Between randomisation and time of followup at Visit 7, about 4 weeks duration

Antidepressants medication initiation by a participant due to depressive episodes over the duration of the study (Visit 2 to Visit 7): (i) Introduction of a new antidepressant (yes / no)

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=26 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Introduction of New Antidepressant	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Between randomisation and time of followup at Visit 7, about 4 weeks duration

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=26 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Increase in Dose of Existing Antidepressant	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Between randomisation and time of followup at Visit 7, about 4 weeks duration

Occurrence of hypo (manic) episodes as defined by a score of \>6 on the Young Mania Rating Scale during study

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=26 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Occurrence of Hypo (Manic) Episodes Measured by the Young Mania Rating Scale	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Between randomisation and time of followup at Visit 7, about 4 weeks duration

Psychiatric inpatient admission of a participant due to depressive episodes during the trial (Visits 2 to 7)

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants randomised to the placebo group will receive one 15-minute IV infusion of 100ml Saline at 4 visits. Placebo / Saline: The placebo group will receive a 100ml infusion of saline at 4 visits during the study	Scopolamine n=26 Participants Participants randomised to the Scopolamine/treatment group will receive one 15-minute IV infusion of Scopolamine at 4 visits. Scopolamine: The treatment group will receive a 100ml infusion of Scopolamine ( dose 4μg/kg) at 4 visits during the study
Admitted to a Psychiatric Inpatient Unit Due to Depressive Episode	1 Participants	2 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Scopolamine

Serious events: 3 serious events

Other events: 25 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=24 participants at risk Participants randomised to the placebo group will receive one 15-minute IV infusion of 100mL Saline at 4 visits.	Scopolamine n=26 participants at risk Participants randomised to the treatment group will receive one 15-minute IV infusion of Scopolamine (dose 4μg/kg) at 4 visits.
Psychiatric disorders Depressed mood	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Psychiatric disorders Emotional distress	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Psychiatric disorders Suspected suicide	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.

Other adverse events

Additional Information

Dr. Alberto Alvarez-Iglesias

University of Galway

Phone: +35391524411

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=24 participants at risk Participants randomised to the placebo group will receive one 15-minute IV infusion of 100mL Saline at 4 visits.	Scopolamine n=26 participants at risk Participants randomised to the treatment group will receive one 15-minute IV infusion of Scopolamine (dose 4μg/kg) at 4 visits.
Gastrointestinal disorders Abdominal hernia	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Abdominal pain upper	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Skin and subcutaneous tissue disorders Acne	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Psychiatric disorders Anxiety	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Aphthous ulcer	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Investigations Blood glucose increased	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Chills	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Investigations Colonoscopy	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Psychiatric disorders Confusional state	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Diarrhoea	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Dizziness	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	61.5% 16/26 • Number of events 29 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Dizziness postural	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Dry mouth	12.5% 3/24 • Number of events 3 • From randomisation through to study completion, an average of about 4 weeks.	50.0% 13/26 • Number of events 18 • From randomisation through to study completion, an average of about 4 weeks.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Reproductive system and breast disorders Endometriosis	8.3% 2/24 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Eye disorders Eye pain	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Fatigue	8.3% 2/24 • Number of events 5 • From randomisation through to study completion, an average of about 4 weeks.	11.5% 3/26 • Number of events 3 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Feeling abnormal	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Vascular disorders Flushing	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Infections and infestations Gingival abscess	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Headache	12.5% 3/24 • Number of events 6 • From randomisation through to study completion, an average of about 4 weeks.	19.2% 5/26 • Number of events 5 • From randomisation through to study completion, an average of about 4 weeks.
Infections and infestations Helminthic infection	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Vascular disorders Hot flush	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Musculoskeletal and connective tissue disorders Joint swelling	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Infections and infestations Lower respiratory tract infection	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Malaise	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Nausea	12.5% 3/24 • Number of events 4 • From randomisation through to study completion, an average of about 4 weeks.	30.8% 8/26 • Number of events 11 • From randomisation through to study completion, an average of about 4 weeks.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	7.7% 2/26 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.
Psychiatric disorders Panic reaction	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Paraesthesia	4.2% 1/24 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	4.2% 1/24 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Infections and infestations Respiratory tract infection	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Restless legs syndrome	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Sensation of foreign body	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Somnolence	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	30.8% 8/26 • Number of events 11 • From randomisation through to study completion, an average of about 4 weeks.
Psychiatric disorders Tension	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	3.8% 1/26 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Tension headache	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	7.7% 2/26 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Thirst	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	11.5% 3/26 • Number of events 5 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Toothache	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Nervous system disorders Tremor	8.3% 2/24 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.	7.7% 2/26 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.
Metabolism and nutrition disorders Type 2 diabetes mellitus	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Infections and infestations Upper respiratory tract infection	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Skin and subcutaneous tissue disorders Urticaria	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
General disorders Vessel puncture site bruise	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Eye disorders Vision blurred	0.00% 0/24 • From randomisation through to study completion, an average of about 4 weeks.	11.5% 3/26 • Number of events 3 • From randomisation through to study completion, an average of about 4 weeks.
Gastrointestinal disorders Vomiting	16.7% 4/24 • Number of events 4 • From randomisation through to study completion, an average of about 4 weeks.	7.7% 2/26 • Number of events 2 • From randomisation through to study completion, an average of about 4 weeks.
Infections and infestations Vulvovaginal candidiasis	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.
Respiratory, thoracic and mediastinal disorders Wheezing	4.2% 1/24 • Number of events 1 • From randomisation through to study completion, an average of about 4 weeks.	0.00% 0/26 • From randomisation through to study completion, an average of about 4 weeks.