Trial Outcomes & Findings for D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia (NCT NCT00237809)

Last Updated: 2017-05-10

Results Overview

The WCST allows the clinician to speculate to the following "frontal" lobe functions: strategic planning, organized searching, utilizing environmental feedback to shift cognitive sets, directing behavior toward achieving a goal, and modulating impulsive responding. The test can be administered to those from 6.5 years to 89 years of age.The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Can be interpreted as: the greater the percentage, the greater the measured ability.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

104 participants

Primary outcome timeframe

12 weeks

Results posted on

2017-05-10

Participant Flow

Subjects were enrolled between 2003 and 2008, with enrollment of subjects in India starting later (2005) and ending in 2008.

132 subjects were screened for eligibility. After screening, eligible subjects were randomized to receive: D-serine+CRT, placebo D-serine+CRT, D-serine + control CRT, or placebo D-serine + control CRT. Randomization was stratified by screening performance IQ. Separate randomization schedules (block size= 4) were generated within IQ stratum.

Participant milestones

Participant milestones
Measure	D-serine Drug /CRT Placebo D-serine/control D-serine : D-serine (30 mg/kg)	Placebo Drug /CRT Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine Drug/CRT D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo Drug/ Placebo CRT Placebo/control
Overall Study STARTED	27	27	24	26
Overall Study COMPLETED	16	17	15	17
Overall Study NOT COMPLETED	11	10	9	9

Reasons for withdrawal

Reasons for withdrawal
Measure	D-serine Drug /CRT Placebo D-serine/control D-serine : D-serine (30 mg/kg)	Placebo Drug /CRT Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine Drug/CRT D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo Drug/ Placebo CRT Placebo/control
Overall Study Lost to Follow-up	11	10	9	9

Baseline Characteristics

D-Serine Treatment of Negative Symptoms and Cognitive Deficits in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : Cog rehab	Total n=104 Participants Total of all reporting groups
Age, Continuous	35.7500 years STANDARD_DEVIATION 8.01889 • n=5 Participants	34.4762 years STANDARD_DEVIATION 8.76139 • n=7 Participants	36.3158 years STANDARD_DEVIATION 9.16547 • n=5 Participants	34.4545 years STANDARD_DEVIATION 9.36420 • n=4 Participants	35.21 years STANDARD_DEVIATION 8.72 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	26 Participants n=21 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	22 Participants n=7 Participants	19 Participants n=5 Participants	19 Participants n=4 Participants	78 Participants n=21 Participants

PRIMARY outcome

Timeframe: 12 weeks

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
Wisconsin Card Sorting Test (WCST)	38.43 percentage of correct responses Standard Deviation 24.07	35.79 percentage of correct responses Standard Deviation 21.57	43.14 percentage of correct responses Standard Deviation 27.06	39.57 percentage of correct responses Standard Deviation 22.31

PRIMARY outcome

Timeframe: 12 weeks

The Hopkins Verbal Learning Test is designed to assess verbal learning and memory (immediate recall, delayed recall, delayed recognition). The assessment takes approximately 5-10 minutes with a 25-minute delay to complete and 2 minutes to score. The greater the score, the greater the measured recall. The score ranges from 0 to 24.

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
Hopkins Verbal Learning Test	20.74 units on a scale Standard Deviation 5.25	19.80 units on a scale Standard Deviation 5.94	20.42 units on a scale Standard Deviation 7.51	21.45 units on a scale Standard Deviation 5.85

PRIMARY outcome

Timeframe: 12 weeks

The Spatial Span subtest of the Wechsler Memory Scale can be used as an indicator of working memory and visuospatial processing. An increase in severity of impairment results in a decrease in Spatial Span Total Score. The range is 1 to 28.

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
Spatial Span- Total Score	13.59 units on a scale Standard Deviation 4.18	13.88 units on a scale Standard Deviation 4.20	13.21 units on a scale Standard Deviation 3.23	13.58 units on a scale Standard Deviation 4.07

PRIMARY outcome

Timeframe: 12 weeks

The PANSS is a handscored instrument. It uses 25 PANSS items organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The PANSS is based on findings that schizophrenia comprises at least two distinct syndromes. The positive syndrome consists of productive symptoms, while the negative syndrome consists of deficit features. This distinction is useful when developing treatment plans because you can focus on the type of symptoms the patient is experiencing. It is also useful when studying the effects of medication (e.g., in clinical drug trials) because it allows you to determine which type of symptoms are being affected. PANSS Total score minimum = 30, maximum = 210. The greater the score, the greater the symptoms.

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
Positive and Negative Syndrome Scale (PANSS)	53.30 units on a scale Standard Deviation 13.58	52.01 units on a scale Standard Deviation 13.34	53.79 units on a scale Standard Deviation 12.76	53.96 units on a scale Standard Deviation 12.43

SECONDARY outcome

Timeframe: 12 weeks

The Heinrichs-Carpenter Quality of Life Scale is a testing device. It has a range of possible scores, 0-126 used to evaluate social functioning \& behavior in patients with schizophrenia-lower scores represent poorer mental health.

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
Heinrichs-Carpenter Quality of Life Scale	67.26 units on a scale Standard Deviation 20.04	68.30 units on a scale Standard Deviation 25.59	63.25 units on a scale Standard Deviation 24.15	63.92 units on a scale Standard Deviation 19.53

SECONDARY outcome

Timeframe: 12 weeks

Simpson-Angus Scale (SAS) is a 10-item rating scale that has been used widely for assessment in both clinical practice and research settings. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The highest possible score is 40.

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
Simpson-Angus Neurological Rating Scale	1.41 units on a scale Standard Deviation 2.53	0.72 units on a scale Standard Deviation 1.73	1.04 units on a scale Standard Deviation 1.27	1.81 units on a scale Standard Deviation 2.25

SECONDARY outcome

Timeframe: 12 weeks

The UCSD Performance-Based Skills Assessment (UPSA) is a role-play test designed to evaluate a person's functional capacity in two selected areas of basic living skills. These areas include Finance and Communication. Subjects being tested utilize props to demonstrate how they perform everyday activities and are assessed on their actual performance. The higher the score, the better the performance of an individual. The scores range from 0 to 100.

Outcome measures

Outcome measures
Measure	D-serine/Control n=27 Participants D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 Participants Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 Participants D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 Participants Placebo/control Cognitive retraining : video
UCSD Performance-Based Skills Assessment (UPSA)	34.19 units on a scale Standard Deviation 9.41	32.80 units on a scale Standard Deviation 10.98	32.60 units on a scale Standard Deviation 13.82	31.39 units on a scale Standard Deviation 10.01

Adverse Events

D-serine/Control

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo/Cog Rehab

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

D-serine/Cog Rehab

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo/Control

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Deepak Cyril D'Souza

Yale University

Phone: 203-932-5711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	D-serine/Control n=27 participants at risk D-serine/control D-serine : D-serine (30 mg/kg)	Placebo/Cog Rehab n=27 participants at risk Placebo/cog rehab Cognitive retraining : Cog rehab	D-serine/Cog Rehab n=24 participants at risk D-serine/cog rehab D-serine : D-serine (30 mg/kg)	Placebo/Control n=26 participants at risk Placebo/control Cognitive retraining : video
Psychiatric disorders Concentration Difficulty	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	11.5% 3/26 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Increased Fatigue	14.8% 4/27 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.	11.1% 3/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	15.4% 4/26 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Sleepiness	22.2% 6/27 • Number of events 15 • Adverse events (serious and other) are reported overall at the month time frame.	25.9% 7/27 • Number of events 8 • Adverse events (serious and other) are reported overall at the month time frame.	25.0% 6/24 • Number of events 12 • Adverse events (serious and other) are reported overall at the month time frame.	34.6% 9/26 • Number of events 20 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Failed Memory	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	15.4% 4/26 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Depression	11.1% 3/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	11.5% 3/26 • Number of events 7 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Tension	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	11.1% 3/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.	11.5% 3/26 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Increased Sleep	29.6% 8/27 • Number of events 13 • Adverse events (serious and other) are reported overall at the month time frame.	18.5% 5/27 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.	12.5% 3/24 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.	23.1% 6/26 • Number of events 9 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Reduced Sleep	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	12.5% 3/24 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.	3.8% 1/26 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Increased Dreams	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	15.4% 4/26 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.
Psychiatric disorders Emotional Indifference	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	3.8% 1/26 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Dystonia	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Rigidity	14.8% 4/27 • Number of events 8 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	12.5% 3/24 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.	26.9% 7/26 • Number of events 12 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Hypokinesia	7.4% 2/27 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	7.7% 2/26 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Hyperkinesia	18.5% 5/27 • Number of events 11 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.	19.2% 5/26 • Number of events 10 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Tremor	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	18.5% 5/27 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.	12.5% 3/24 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.	19.2% 5/26 • Number of events 14 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Akathesia	7.4% 2/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	11.5% 3/26 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Epileptic Seizure	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Nervous system disorders Paraesthesias	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Eye disorders Accommodation Distance	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Gastrointestinal disorders Increased Salivation	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	7.7% 2/26 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.
Gastrointestinal disorders Reduced Salivation	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	7.7% 2/26 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.
Gastrointestinal disorders Nausea	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	7.7% 2/26 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.
Gastrointestinal disorders Diarrhea	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	15.4% 4/26 • Number of events 4 • Adverse events (serious and other) are reported overall at the month time frame.
Gastrointestinal disorders Constipation	11.1% 3/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	3.8% 1/26 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.
Renal and urinary disorders Micturition Distance	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Renal and urinary disorders Polyuria	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	7.7% 2/26 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.
General disorders Dizziness	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	8.3% 2/24 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	15.4% 4/26 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.
General disorders Polyps / Tachycardia	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	3.8% 1/26 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.
General disorders Increased Sweat	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
General disorders Rash	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
General disorders Pruritus	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Eye disorders Photosensitivity	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	3.8% 1/26 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.
Eye disorders Increased Pigmentation	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Metabolism and nutrition disorders Weight Increase	7.4% 2/27 • Number of events 2 • Adverse events (serious and other) are reported overall at the month time frame.	14.8% 4/27 • Number of events 6 • Adverse events (serious and other) are reported overall at the month time frame.	12.5% 3/24 • Number of events 5 • Adverse events (serious and other) are reported overall at the month time frame.	30.8% 8/26 • Number of events 12 • Adverse events (serious and other) are reported overall at the month time frame.
Metabolism and nutrition disorders Weight Decrease	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	3.7% 1/27 • Number of events 1 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Reproductive system and breast disorders Menorrhagia	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Reproductive system and breast disorders Amenorrhoea	11.1% 3/27 • Number of events 8 • Adverse events (serious and other) are reported overall at the month time frame.	7.4% 2/27 • Number of events 20 • Adverse events (serious and other) are reported overall at the month time frame.	4.2% 1/24 • Number of events 3 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Reproductive system and breast disorders Galactorrhoea	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.
Reproductive system and breast disorders Increased Sexual Desire	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/27 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/24 • Adverse events (serious and other) are reported overall at the month time frame.	0.00% 0/26 • Adverse events (serious and other) are reported overall at the month time frame.