Trial Outcomes & Findings for PRX-00023 Therapy in Localization-Related Epilepsy (NCT NCT01281956)

NCT ID: NCT01281956

Last Updated: 2018-12-07

Results Overview

Participants used a seizure calendar to record the number of seizures that occurred during the three month treatment period, i.e., while participants were either on PRX-0023 or Placebo. Seizure frequency was calculated as the total number of seizures occurring during each three month period. For each period a mean was calculated across subjects.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Three months

Results posted on

2018-12-07

Participant Flow

Two participants that were consented to the protocol, did not participate in the study procedures. One participant was screened but was not randomized and did not receive study drug or placebo and one participant did not return for screening visit.

Participant milestones

Participant milestones
Measure	Placebo Then PRX Participants with epilepsy receiving placebo during the first period followed by PRX during the second period	PRX Then Placebo Participants with epilepsy receiving PRX during the first period followed by Placebo during the second period
1st Intervention (3 Months) STARTED	5	5
1st Intervention (3 Months) COMPLETED	5	5
1st Intervention (3 Months) NOT COMPLETED	0	0
2nd Intervention (3 Months) STARTED	5	5
2nd Intervention (3 Months) COMPLETED	4	5
2nd Intervention (3 Months) NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Then PRX Participants with epilepsy receiving placebo during the first period followed by PRX during the second period	PRX Then Placebo Participants with epilepsy receiving PRX during the first period followed by Placebo during the second period
2nd Intervention (3 Months) Withdrawal by Subject	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants Enrolled in Study n=10 Participants All participants enrolled in the study
Age, Categorical <=18 years	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=10 Participants
Age, Categorical >=65 years	0 Participants n=10 Participants
Age, Continuous	40 years STANDARD_DEVIATION 12.16 • n=10 Participants
Sex: Female, Male Female	3 Participants n=10 Participants
Sex: Female, Male Male	7 Participants n=10 Participants

PRIMARY outcome

Timeframe: Three months

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Seizure Frequency in the Active and Placebo Periods	66.6 number of seizures Standard Deviation 93.3	54.3 number of seizures Standard Deviation 79.7

SECONDARY outcome

Timeframe: Three months

Participants used a seizure calendar to record the number of seizures that occurred during each three month treatment period, i.e., while participants were either on PRX-0023 or Placebo. Seizure rate was calculated as the total number of seizures occurring during the three month period. The number of participants with \>50% lower seizure frequency during the active compared with the placebo period was determined.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo Participants with epilepsy receiving Placebo
Number of Participants With > 50% Lower Seizure Rate on PRX-0023.	0 Participants	—

SECONDARY outcome

Timeframe: Three months

Participants were administered the Hamilton Anxiety Rating Scale (HAM-A) at the end of each three month treatment period, i.e., while participants were either on PRX-0023 or Placebo. The HAM-A measures an individual's severity of anxiety symptoms. The scale consists of 14 parameters, each defined by a series of symptoms. Each group of symptoms is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \</=17 indicates mild anxiety, 18-24 mild to moderate anxiety and 25-30 moderate to severe anxiety and \>30 severe anxiety.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Mean Score on the Hamilton Anxiety Rating Scale at the End of the Active and Placebo Periods.	5.1 score on a scale Standard Deviation 5.0	5.7 score on a scale Standard Deviation 5.7

SECONDARY outcome

Timeframe: Three months

The Hamilton Depression Rating Scale (HAM-D) was administered to participants at the end of each treatment period. The HAM-D is a multiple item questionnaire used to provide an indication of depression. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Although the HAM-D form lists 21 items, the scoring is based on the first 17 items. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored from 0-2 with 0 = absent and 2 = frequent or severe. Scores range from 0 to 50 with a score of 0-7 representing normal and a score \>/= 23 representing very severe depression.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Mean Score on the Hamilton Depression Rating Scale at the End of the Active and Placebo Periods	5.3 score on a scale Standard Deviation 3.9	8.6 score on a scale Standard Deviation 12.8

SECONDARY outcome

Timeframe: Three months

Population: Unable to complete the delayed recall in one participant in the placebo arm.

The HVLT-R is a word-list learning and memory test.The participant is read a list of words and asked to recall as many as possible, without regard to the order in which they were read.The list is read three times with recall requested after each presentation (immediate recall) and after a delay (delayed recall). Individual test results are compared to others of the same age (+/-5 years).Test results are presented as T-scores which are conventionally used in neuropsychology. The participant's raw scores are compared to a population expected raw score, for a particular age group. That score is converted to a T-score.The interpretation of these T-scores is such that 50 is representative of the normal score in that age group in the general population. The standard deviation of these distributions are 10 units. Therefore, a score between 30-40 is considered mildly impaired, 20-30 is indicative of severe problems with learning and memory and a score of 60-70 indicates a very good memory.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Mean Score on the Hopkins Verbal Learning Test-Revised (HVLT-R) at the End of the Active and Placebo Periods Immediate Recall	34.8 psychometric T-score Standard Deviation 13.8	41.6 psychometric T-score Standard Deviation 10.1
Mean Score on the Hopkins Verbal Learning Test-Revised (HVLT-R) at the End of the Active and Placebo Periods Delayed Recall	33.3 psychometric T-score Standard Deviation 14.1	39.2 psychometric T-score Standard Deviation 10.8

SECONDARY outcome

Timeframe: Three months

Population: Unable to complete the delayed recall in one subject in the placebo arm

The BVMT-R is a test of memory for visual information. Participants are shown a page with several geometric designs arranged in a 2x3 matrix and asked to study the designs. After the page is shown for a brief period the participant is asked to draw each figure.The same page is shown three times with recall requested after each presentation (immediate recall) and after a delay (delayed recall). Individual test results are compared to other people the same age (+/- 5 years).Test results are presented as T-scores which are conventionally used in neuropsychology. The participant's raw scores are compared to a population expected raw score, for a particular age group.That score is converted to a T-score.The interpretation of these T-scores is such that 50 is representative of the normal score in that age group in the general population.The standard deviation of these distributions are 10 units. A score of 30-40 is considered mildly impaired, 20-30 is indicative of severe problems

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
The Mean Score on the Brief Visuospatial Memory Test-Revised (BVMT-R), at the End of the Active and Placebo Period. Immediate Recall	37.4 psychometric T-score Standard Deviation 9.7	39.0 psychometric T-score Standard Deviation 9.9
The Mean Score on the Brief Visuospatial Memory Test-Revised (BVMT-R), at the End of the Active and Placebo Period. Delayed Recall	38.0 psychometric T-score Standard Deviation 11.9	37.4 psychometric T-score Standard Deviation 15.4

SECONDARY outcome

Timeframe: Three months

Population: Missing data for one participant in the Placebo group

The Columbia Suicide Severity Rating Scale (C-SSRS) was administered to subjects at the end of each treatment period. The C-SSRS, is a suicidal ideation and behavior rating scale which evaluates suicide risk. The assessment rates an individual's degree of suicidal ideation on a scale, ranging from 0 to 6 as follows: 0 = No suicide ideation; 1 = Wish to be dead; 2 = Non-Specific Active Suicidal Thoughts; 3 = Active Suicidal Ideation with any methods (No Plan) without intent to act; 4 = Active Suicidal Ideation with some intent to act, without specific plan; 5 = Active Suicidal Ideation with specific plan and intent; and 6 = Actual Suicide Attempt

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=9 Participants Participants with epilepsy receiving Placebo
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 0	9 Participants	8 Participants
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 1	0 Participants	1 Participants
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 2	0 Participants	0 Participants
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 3	0 Participants	0 Participants
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 4	0 Participants	0 Participants
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 5	0 Participants	0 Participants
Mean Score on the Columbia Suicide Severity Rating Scale at the End of the Active and Placebo Periods 6	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Three months

A clinical examination of the nervous system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Results of Clinical Examination of the Nervous System at the End of the Active and Placebo Treatment Periods 0	8 Participants	9 Participants
Results of Clinical Examination of the Nervous System at the End of the Active and Placebo Treatment Periods 1	0 Participants	0 Participants
Results of Clinical Examination of the Nervous System at the End of the Active and Placebo Treatment Periods 2	1 Participants	1 Participants
Results of Clinical Examination of the Nervous System at the End of the Active and Placebo Treatment Periods 3	0 Participants	0 Participants
Results of Clinical Examination of the Nervous System at the End of the Active and Placebo Treatment Periods 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Three months

A clinical examination of the respiratory system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Results of Clinical Examination of the Respiratory System at the End of the Active and Placebo Treatment Periods 0	8 Participants	10 Participants
Results of Clinical Examination of the Respiratory System at the End of the Active and Placebo Treatment Periods 1	1 Participants	0 Participants
Results of Clinical Examination of the Respiratory System at the End of the Active and Placebo Treatment Periods 2	0 Participants	0 Participants
Results of Clinical Examination of the Respiratory System at the End of the Active and Placebo Treatment Periods 3	0 Participants	0 Participants
Results of Clinical Examination of the Respiratory System at the End of the Active and Placebo Treatment Periods 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Three months

A clinical examination of the cardiovascular system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Results of Clinical Examination of the Cardiovascular System at the End of the Active and Placebo Treatment Periods 0	8 Participants	9 Participants
Results of Clinical Examination of the Cardiovascular System at the End of the Active and Placebo Treatment Periods 1	1 Participants	1 Participants
Results of Clinical Examination of the Cardiovascular System at the End of the Active and Placebo Treatment Periods 2	0 Participants	0 Participants
Results of Clinical Examination of the Cardiovascular System at the End of the Active and Placebo Treatment Periods 3	0 Participants	0 Participants
Results of Clinical Examination of the Cardiovascular System at the End of the Active and Placebo Treatment Periods 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Three months

A clinical examination of the musculoskeletal system was administered by a physician to subjects at the end of each three month treatment period, i.e., while the participant was on PRX-0023 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0 = normal examination; 1 = Observation only; patient asymptomatic; 2 = Patient reports complaint associated with finding but no dysfunction; 3 = Patient reports some impairment of daily function associated with finding; 4 = Patient unable to carry out usual activities due to dysfunction associated with finding.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Results of Clinical Examination of the Musculoskeletal System at the End of the Active and Placebo Treatment Periods 0	9 Participants	9 Participants
Results of Clinical Examination of the Musculoskeletal System at the End of the Active and Placebo Treatment Periods 1	0 Participants	1 Participants
Results of Clinical Examination of the Musculoskeletal System at the End of the Active and Placebo Treatment Periods 2	0 Participants	0 Participants
Results of Clinical Examination of the Musculoskeletal System at the End of the Active and Placebo Treatment Periods 3	0 Participants	0 Participants
Results of Clinical Examination of the Musculoskeletal System at the End of the Active and Placebo Treatment Periods 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Three months

A Complete Blood Count (CBC) was administered at the end of each three month treatment period. A complete blood count test measures several components and features of your blood, including: Red blood cells (which carry oxygen), White blood cells (which fight infection), Hemoglobin (the oxygen-carrying protein in red blood cells), Hematocrit (the proportion of red blood cells to the fluid component (plasma) in your blood), Platelets, (which help with blood clotting). Abnormal increases or decreases in cell counts as revealed in a complete blood count may indicate an underlying medical condition, i.e., anemia (abnormal red blood cells, hemoglobin, and/or hematocrit), leucopenia (a decrease in white blood cells), leucocytosis (an increase in white blood cells), and thrombocytosis (an increase in platelets). Results were classified as either normal or abnormal.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Number of Subjects With an Abnormal CBC Result at the End of the Active and Placebo Periods anemia	2 Participants	1 Participants
Number of Subjects With an Abnormal CBC Result at the End of the Active and Placebo Periods leucopenia	2 Participants	1 Participants
Number of Subjects With an Abnormal CBC Result at the End of the Active and Placebo Periods leucocytosis	2 Participants	3 Participants
Number of Subjects With an Abnormal CBC Result at the End of the Active and Placebo Periods thrombocytosis	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Three months

The number of subjects with abnormal clinical chemistry labs which is defined as a value outside of the NIH Clinical Center normal range.

Outcome measures

Outcome measures
Measure	PRX-0023 n=9 Participants Participants with epilepsy receiving PRX-0023	Placebo n=10 Participants Participants with epilepsy receiving Placebo
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods electrolyte abnormality	4 Participants	4 Participants
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods hyperglycemia	2 Participants	1 Participants
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods elevated liver function < 2 x normal	3 Participants	3 Participants
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods elevated liver function > 2 x normal	1 Participants	0 Participants
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods abnormal urinalysis	3 Participants	4 Participants
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods elevated uric acid	0 Participants	1 Participants
Number of Subjects With Abnormal Clinical Chemistry Labs at the End of the Active and Placebo Periods elevated BUN or Creatinine	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Three months

Population: Missing data

An electrocardiogram was administered to participants at the end of each treatment period, i.e., at the end of the PRX-0023 and Placebo treatment periods. The number of abnormal ECG readings was noted in this measure.

Outcome measures

Outcome measures
Measure	PRX-0023 n=8 Participants Participants with epilepsy receiving PRX-0023	Placebo n=9 Participants Participants with epilepsy receiving Placebo
Number of Subjects With an Abnormal ECG Result at the End of the Active and Placebo Periods	2 Participants	3 Participants

Adverse Events

PRX-0023

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. William Theodore

National Institutes of Health

Phone: 301-496-1505

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	PRX-0023 n=9 participants at risk Participants with epilepsy receiving PRX-0023	Placebo n=10 participants at risk Participants with epilepsy receiving placebo
Infections and infestations Upper Respiratory Infection	22.2% 2/9 • Number of events 2 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Skin and subcutaneous tissue disorders Itching	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	20.0% 2/10 • Number of events 2 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Gastrointestinal disorders Diarrhea	11.1% 1/9 • Number of events 2 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Skin and subcutaneous tissue disorders Small bumps on back	11.1% 1/9 • Number of events 3 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Skin and subcutaneous tissue disorders Bumps at IV site	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Gastrointestinal disorders GI Upset	11.1% 1/9 • Number of events 2 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Nervous system disorders Gait Imbalance	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Hepatobiliary disorders Elevated liver function test >2x normal	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Skin and subcutaneous tissue disorders Change in nails and hair	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Infections and infestations Stomach flu	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Musculoskeletal and connective tissue disorders Injury following seizure	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Nervous system disorders Headache	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	20.0% 2/10 • Number of events 2 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Skin and subcutaneous tissue disorders Bug bites	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Nervous system disorders Lethargy	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	40.0% 4/10 • Number of events 4 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Gastrointestinal disorders Weight gain	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Gastrointestinal disorders Increased appetite	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 2 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Infections and infestations Achy and sweaty	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Respiratory, thoracic and mediastinal disorders Chest pressure during sleep	0.00% 0/9 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	10.0% 1/10 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).
Eye disorders Eye pain	11.1% 1/9 • Number of events 1 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).	0.00% 0/10 • Adverse Events were collected following baseline history and physical examination and continued until study completion. Study duration was 42-46 weeks (+/- 4 weeks).