Trial Outcomes & Findings for Reclaim Deep Brain Stimulation Clinical Study for Treatment-Resistant Depression (NCT NCT00837486)

Last Updated: 2015-05-28

Results Overview

Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Baseline to 16 weeks

Results posted on

2015-05-28

Participant Flow

Participant milestones

Participant milestones
Measure	Active Group-Active Stimulation Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation Receive sham stimulation during the first 16 weeks after device implant.
Blinded-treatment Phase STARTED	16	14
Blinded-treatment Phase COMPLETED	15	14
Blinded-treatment Phase NOT COMPLETED	1	0
Long-term Follow-up Phase - Open Label STARTED	29	0
Long-term Follow-up Phase - Open Label COMPLETED	24	0
Long-term Follow-up Phase - Open Label NOT COMPLETED	5	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Group-Active Stimulation Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation Receive sham stimulation during the first 16 weeks after device implant.
Blinded-treatment Phase Physician Decision	1	0
Long-term Follow-up Phase - Open Label Physician Decision	2	0
Long-term Follow-up Phase - Open Label Withdrawal by Subject	2	0
Long-term Follow-up Phase - Open Label Death	1	0

Baseline Characteristics

Reclaim Deep Brain Stimulation Clinical Study for Treatment-Resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Group-Active Stimulation n=16 Participants Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation n=14 Participants Receive sham stimulation during the first 16 weeks after device implant.	Total n=30 Participants Total of all reporting groups
Age, Continuous	46.6 years STANDARD_DEVIATION 14.4 • n=5 Participants	48.9 years STANDARD_DEVIATION 8.9 • n=7 Participants	47.7 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	14 participants n=7 Participants	30 participants n=5 Participants
Baseline depression score	37.0 units on a scale STANDARD_DEVIATION 5.1 • n=5 Participants	36.4 units on a scale STANDARD_DEVIATION 3.3 • n=7 Participants	36.7 units on a scale STANDARD_DEVIATION 4.3 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 16 weeks

Population: 29 of the 30 subjects are included in this analysis. One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.

Outcome measures

Outcome measures
Measure	Active Group-Active Stimulation n=15 Participants Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation n=14 Participants Receive sham stimulation during the first 16 weeks after device implant.
Responders	3 participants	2 participants

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.

Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Improvement is measured by the groups' mean percent change in MADRS score. An improvement is represented by a decline in MADRS (a negative percent change).

Outcome measures

Outcome measures
Measure	Active Group-Active Stimulation n=15 Participants Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation n=14 Participants Receive sham stimulation during the first 16 weeks after device implant.
Depression Change	-19.6 percentage change from baseline Standard Deviation 34.9	-24.6 percentage change from baseline Standard Deviation 28.8

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.

Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF); total score can range from 0 to 100 with higher scores indicating a better quality of life. Improvement is measured by the groups' mean change in Q-LES-Q-SF score. An improvement is represented by an increase in Q-LES-Q-SF (a positive change).

Outcome measures

Outcome measures
Measure	Active Group-Active Stimulation n=15 Participants Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation n=14 Participants Receive sham stimulation during the first 16 weeks after device implant.
Quality of Life Change	10.2 change from baseline score Standard Deviation 24.8	9.8 change from baseline score Standard Deviation 18.8

OTHER_PRE_SPECIFIED outcome

Timeframe: at the 24-month visit

Population: 29 participants started the the Long-Term Follow-up Phase and 24 completed the phase, but all 30 enrolled participants are included in the analysis. Participants that withdrew early are counted as non-responders.

This measure is for long-term, open-label stimulation. Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response. All enrolled participants are included in the analysis, even if they withdrew early. Participants that withdrew early are counted as non-responders.

Outcome measures

Outcome measures
Measure	Active Group-Active Stimulation n=30 Participants Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation Receive sham stimulation during the first 16 weeks after device implant.
Long-term Open-label Responders	7 participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: from enrollment to study closure (average follow-up of 36 months)

Population: All enrolled participants are included in the analysis.

Adverse events related to the device, implant procedure, and/or stimulation are reported. Events with a prevalence of greater than 5% of subjects are reported. This measure describes the experience of all study participants (both Active and Control Groups combined), and includes the operative, blinded-treatment,and the long-term open-label follow-up phases combined. Active Group participants began therapy after randomization, while Control Group participants began therapy after 16 weeks of sham stimulation.

Outcome measures

Outcome measures
Measure	Active Group-Active Stimulation n=30 Participants Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation Receive sham stimulation during the first 16 weeks after device implant.
Therapy-related Adverse Events Stimulation - Nausea	2 participants	—
Therapy-related Adverse Events Stimulation - Thinking abnormal	2 participants	—
Therapy-related Adverse Events Stimulation - Weight increased	2 participants	—
Therapy-related Adverse Events Device - Implant site pain	7 participants	—
Therapy-related Adverse Events Device - Paraesthesia	4 participants	—
Therapy-related Adverse Events Procedure - Implant site pain	8 participants	—
Therapy-related Adverse Events Procedure - Implant site infection	5 participants	—
Therapy-related Adverse Events Procedure - Dermatitis contact	2 participants	—
Therapy-related Adverse Events Procedure - Face oedema	2 participants	—
Therapy-related Adverse Events Procedure - Headache	2 participants	—
Therapy-related Adverse Events Procedure - Hypersensitivity	2 participants	—
Therapy-related Adverse Events Stimulation - Insomnia	15 participants	—
Therapy-related Adverse Events Stimulation - Depression	8 participants	—
Therapy-related Adverse Events Stimulation - Hypomania	8 participants	—
Therapy-related Adverse Events Stimulation - Irritability	8 participants	—
Therapy-related Adverse Events Stimulation - Anxiety	7 participants	—
Therapy-related Adverse Events Stimulation - Fatigue	6 participants	—
Therapy-related Adverse Events Stimulation - Headache	6 participants	—
Therapy-related Adverse Events Stimulation - Agitation	5 participants	—
Therapy-related Adverse Events Stimulation - Sleep disorder	5 participants	—
Therapy-related Adverse Events Stimulation - Disturbance in attention	4 participants	—
Therapy-related Adverse Events Stimulation - Suicidal ideation	4 participants	—
Therapy-related Adverse Events Stimulation - Disinhibition	3 participants	—
Therapy-related Adverse Events Stimulation - Memory impairment	3 participants	—
Therapy-related Adverse Events Stimulation - Paraesthesia	3 participants	—
Therapy-related Adverse Events Stimulation - Energy increased	2 participants	—
Therapy-related Adverse Events Stimulation - Impulsive behaviour	2 participants	—

Adverse Events

Active Group-Active Stimulation

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Control Group-Sham Stimulation

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active Group-Active Stimulation n=16 participants at risk Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation n=14 participants at risk Receive sham stimulation during the first 16 weeks after device implant.
Psychiatric disorders Depression	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	21.4% 3/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Suicidal ideation	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Disinhibition	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Vascular disorders Femoral arterial stenosis	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Wound infection staphylococcal	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Injury, poisoning and procedural complications Neurostimulator protrusion	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.

Other adverse events

Additional Information

Eric Williamson, Clinical Evidence Specialist

Medtronic Neuromodulation

Phone: 763-526-7982

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restrictions on the PI allow for the sponsor to review results communications prior to public release and to embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to sponsor for review. The sponsor is also allowed to require changes for technical correctness and to protect confidential information, copyrightable or patentable material; and when reasonably requested, extend the embargo up to an additional 90 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Active Group-Active Stimulation n=16 participants at risk Receive active stimulation during the first 16 weeks after device implant.	Control Group-Sham Stimulation n=14 participants at risk Receive sham stimulation during the first 16 weeks after device implant.
General disorders Implant site pain	25.0% 4/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	14.3% 2/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Depression	25.0% 4/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Insomnia	25.0% 4/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	21.4% 3/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Injury, poisoning and procedural complications Fall	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	21.4% 3/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
General disorders Fatigue	18.8% 3/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Vascular disorders Hypertension	18.8% 3/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Irritability	18.8% 3/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Suicidal ideation	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Headache	12.5% 2/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Influenza	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Disinhibition	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Hypomania	12.5% 2/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Upper respiratory tract infection	12.5% 2/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
General disorders Drug withdrawal syndrome	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Gastroenteritis viral	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Sleep disorder	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Tremor	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Localised infection	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	14.3% 2/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Reproductive system and breast disorders Adnexa uteri mass	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Musculoskeletal and connective tissue disorders Bunion	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Cognitive disorder	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Gastrointestinal disorders Dysphagia	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
General disorders Energy increased	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Eye disorders Eye pain	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Hypersomnia	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Hyporeflexia	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Mania	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Eye disorders Ocular hyperaemia	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Somnolence	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Gastrointestinal disorders Toothache	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Transient ischaemic attack	6.2% 1/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	0.00% 0/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
General disorders Allodynia	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Injury, poisoning and procedural complications Animal bite	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Injury, poisoning and procedural complications Back injury	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Balance disorder	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Gastrointestinal disorders Constipation	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Early morning awakening	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Fungal infection	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Reproductive system and breast disorders Menstruation irregular	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Infections and infestations Nasopharyngitis	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Paraesthesia	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Psychiatric disorders Purging	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Nervous system disorders Restless legs syndrome	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Ear and labyrinth disorders Tinnitus	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/16 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.	7.1% 1/14 • 16 weeks Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.