Trial Outcomes & Findings for Study of Therapeutic Options for Subjects Discontinuing Efalizumab and Experiencing Disease Recurrence (NCT NCT01079988)

NCT ID: NCT01079988

Last Updated: 2014-02-27

Results Overview

The PGA response was classified according to the following categories by changes in all clinical signs and symptoms as compared to baseline: Cleared: Remission except for residual manifestations such as mild erythema (100% improvement) Excellent: Improvement of 75%-99% except for residual manifestations such as mild erythema Good: Improvement of 50%-74%

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 41 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2014-02-27

Participant Flow

Study Initiation Date: 24 February 2004 (first patient, first visit) Study Completion Date: 21 December 2004 (last patient, last visit) Study Centres: 9 clinical centres in Canada

Subjects who satisfied the study's entry criteria were assigned to receive one of five treatment regimens involving accepted therapies for moderate to severe psoriasis

Participant milestones

Measure	Cyclosporin Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Retinoids Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Systemic Corticosteroids Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Methotrexate Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Systemic Corticosteroids/Methotrexate Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.
Overall Study STARTED	10	1	8	20	2
Overall Study COMPLETED	9	1	8	17	1
Overall Study NOT COMPLETED	1	0	0	3	1

Reasons for withdrawal

Measure	Cyclosporin Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Retinoids Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Systemic Corticosteroids Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Methotrexate Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Systemic Corticosteroids/Methotrexate Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.
Overall Study Lost to Follow-up	0	0	0	1	0
Overall Study Lack of Efficacy	1	0	0	0	0
Overall Study Other	0	0	0	2	1

Baseline Characteristics

Study of Therapeutic Options for Subjects Discontinuing Efalizumab and Experiencing Disease Recurrence

Baseline characteristics by cohort

Measure	Cyclosporin n=10 Participants Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Retinoids n=1 Participants Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Systemic Corticosteroids n=8 Participants Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Methotrexate n=20 Participants Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Systemic Corticosteroids/Methotrexate n=2 Participants Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.	Total n=41 Participants Total of all reporting groups
Age, Continuous	43 years STANDARD_DEVIATION 12 • n=5 Participants	41 years n=7 Participants	44 years STANDARD_DEVIATION 11 • n=5 Participants	49 years STANDARD_DEVIATION 10 • n=4 Participants	47 years STANDARD_DEVIATION 3 • n=21 Participants	46 years STANDARD_DEVIATION 11 • n=10 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants	1 Participants n=21 Participants	16 Participants n=10 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants	1 Participants n=21 Participants	25 Participants n=10 Participants
Region of Enrollment Canada	10 participants n=5 Participants	1 participants n=7 Participants	8 participants n=5 Participants	20 participants n=4 Participants	2 participants n=21 Participants	41 participants n=10 Participants

PRIMARY outcome

Timeframe: 12 weeks

The PGA response was classified according to the following categories by changes in all clinical signs and symptoms as compared to baseline:

Cleared: Remission except for residual manifestations such as mild erythema (100% improvement) Excellent: Improvement of 75%-99% except for residual manifestations such as mild erythema Good: Improvement of 50%-74%

Outcome measures

Measure	Cyclosporin n=10 Participants Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Retinoids n=1 Participants Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Systemic Corticosteroids n=8 Participants Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Methotrexate n=20 Participants Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Systemic Corticosteroids/Methotrexate n=2 Participants Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.
Physician's Global Assessment (PGA) of Change Over Time (Good or Better)	7 participants	0 participants	2 participants	9 participants	0 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: One patient withdrew

The PGPA consisted of a single self-explanatory item:

On a scale from 0 to 10, with 0 being no psoriasis and 10 the worst psoriasis that you can imagine, please rate the state of your psoriasis right now.

Note: Consider only your skin condition and do not consider other aspects that may be related to your psoriasis (such as psoriatic arthritis).

Outcome measures

Measure	Cyclosporin n=10 Participants Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Retinoids n=1 Participants Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Systemic Corticosteroids n=8 Participants Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Methotrexate n=19 Participants Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Systemic Corticosteroids/Methotrexate n=2 Participants Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.
Patient's Global Psoriasis Assessment (PGPA)	5.1 PGPA score Standard Deviation 2.4	4.0 PGPA score	5.5 PGPA score Standard Deviation 2.8	4.8 PGPA score Standard Deviation 2.7	4.5 PGPA score Standard Deviation 0.7

Adverse Events

Cyclosporin

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Retinoids

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Systemic Corticosteroids

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Methotrexate

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Systemic Corticosteroids/Methotrexate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cyclosporin n=10 participants at risk Starting dose 4.0 - 5.1 mg/kg/day until clinical improvement. Upon clinical improvement, cyclosporin dose to be tapered by 50% every two weeks.	Retinoids n=1 participants at risk Starting dose 25 - 50 mg/day until clinical improvement. Upon clinical improvement, retinoid dose to be reduced by 50%. Thereafter, treatment to be continued for 8 weeks and then stopped.	Systemic Corticosteroids n=8 participants at risk Starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, corticosteroids to be weaned by 50% every 2 weeks.	Methotrexate n=20 participants at risk Starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, methotrexate dose to be reduced by 25% every two weeks.	Systemic Corticosteroids/Methotrexate n=2 participants at risk Corticosteroid starting dose 0.25 - 0.5 mg/kg/day until clinical improvement. Upon clinical improvement, corticosteroid dose to be reduced by 50%. Thereafter, to be weaned by 50% every 2 weeks. Methotrexate starting dose 20 - 25 mg per week until clinical improvement. Upon clinical improvement, dose to be reduced by 25%. Thereafter, to be reduced by 25% every two weeks.
Infections and infestations Influenza	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	10.0% 2/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Nasopharyngitis	20.0% 2/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Upper respiratory tract infection	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	10.0% 2/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Urinary tract infection	20.0% 2/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Furuncle	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Herpes zoster ophthalmic	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Pneumonia	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Rhinitis	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Infections and infestations Sinusitis	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Gastritis	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Nausea	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Abdominal pain	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Anal fissure	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Glossodynia	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Gastrointestinal disorders Tongue disorder	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Musculoskeletal and connective tissue disorders Muscle cramp	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Nervous system disorders Headache	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	25.0% 2/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Nervous system disorders Paraesthesia	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Investigations Alanine aminotransferase increased	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Investigations Blood glucose increased	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Investigations Blood pressure increased	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Investigations Blood urea increased	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
General disorders Fatigue	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
General disorders Rigors	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Respiratory, thoracic and mediastinal disorders Chronic obstructive airways disease	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Injury, poisoning and procedural complications Muscle strain	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Psychiatric disorders Restlessness	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	12.5% 1/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	5.0% 1/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.
Vascular disorders Hypertension	10.0% 1/10 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/1 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/8 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/20 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.	0.00% 0/2 • Adverse events were monitored throughout the study Information about adverse events was obtained at study visits following physical examination, through spontaneous reports by the subjects and through questioning of the subjects. Adverse event data could also be obtained from subject diary cards, but such information had to be reviewed and assessed medically before it was transcribed to the CRF.

Additional Information

Merck KGaA Communication Center

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Phone: +49-6151-72-5200

Email: service@merckgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER