Trial Outcomes & Findings for Treating Chronic Insomnia in Breast Cancer Patients (NCT NCT00337272)

Last Updated: 2011-08-22

Results Overview

Total time in bed is calculated as the time the subject got out of bed minus the time the subject went to bed. The total sleep time is reported by the subject. Percent sleep efficiency is calulated as 100\*(total sleep time divided by total time in bed).

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

16 participants

Primary outcome timeframe

Every morning during the screening, treatment, and withdrawal periods

Results posted on

2011-08-22

Participant Flow

10 community oncology research sites across the United States within Accelerated Community Oncology Research Network (ACORN) participated in this study. Enrollment started in August 2006 and closed in August 2008.

After consent, subjects underwent a 2 week screening period to see if they met the criteria for insomnia and to assess compliance with daily Interactive Voice Recognition System (IVRS) calls.

Participant milestones

Participant milestones
Measure	1 (Placebo) Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Screening Period (Pre-randomization) STARTED	22	0
Screening Period (Pre-randomization) COMPLETED	16	0
Screening Period (Pre-randomization) NOT COMPLETED	6	0
Treatment Period STARTED	7	9
Treatment Period Randomization	7	9
Treatment Period COMPLETED	6	7
Treatment Period NOT COMPLETED	1	2
Withdrawal Period STARTED	6	7
Withdrawal Period COMPLETED	6	6
Withdrawal Period NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	1 (Placebo) Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Screening Period (Pre-randomization) Withdrawal by Subject	2	0
Screening Period (Pre-randomization) Non-compliance	1	0
Screening Period (Pre-randomization) Screen failure	3	0
Treatment Period Non-compliance	1	1
Treatment Period Withdrawal by Subject	0	1
Withdrawal Period Non-compliance	0	1

Baseline Characteristics

Treating Chronic Insomnia in Breast Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 (Placebo) n=7 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=9 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	51.69 Years STANDARD_DEVIATION 5.98 • n=5 Participants	49.11 Years STANDARD_DEVIATION 6.78 • n=7 Participants	50.24 Years STANDARD_DEVIATION 6.37 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every morning during the screening, treatment, and withdrawal periods

Population: Screening period: 14 patients with 6 treated with Placebo and 8 with Ramelteon. Treatment period: 13 patients with 5 treated with Placebo and 8 with Ramelteon. Withdrawal period: 10 patients with 4 treated with Placebo and 6 with Ramelteon.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=8 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Sleep Efficiency Screening Period	59.62 Percent sleep efficiency Standard Deviation 16.72	70.16 Percent sleep efficiency Standard Deviation 12.55
Sleep Efficiency Treatment Period	72.09 Percent sleep efficiency Standard Deviation 9.38	71.26 Percent sleep efficiency Standard Deviation 14.54
Sleep Efficiency Withdrawal Period	75.87 Percent sleep efficiency Standard Deviation 11.85	67.48 Percent sleep efficiency Standard Deviation 14.19

SECONDARY outcome

Timeframe: Every morning during the screening, treatment, and withdrawal periods

The subject reports how many hours of sleep she got.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=8 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Quantitative Sleep Parameters - Total Sleep Time Screening Period	5.02 Hours Standard Deviation 1.62	5.27 Hours Standard Deviation 0.83
Quantitative Sleep Parameters - Total Sleep Time Treatment Period	5.94 Hours Standard Deviation 1.20	5.62 Hours Standard Deviation 0.79
Quantitative Sleep Parameters - Total Sleep Time Withdrawal Period	5.57 Hours Standard Deviation 0.50	5.11 Hours Standard Deviation 0.87

SECONDARY outcome

Timeframe: Every morning during the screening, treatment, and withdrawal periods

The subject reports how many times she woke up during the night.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=8 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Quantitative Sleep Parameters - Number of Awakenings Screening Period	2.62 Awakenings Standard Deviation 0.46	2.66 Awakenings Standard Deviation 1.10
Quantitative Sleep Parameters - Number of Awakenings Treatment Period	2.28 Awakenings Standard Deviation 0.37	2.76 Awakenings Standard Deviation 1.70
Quantitative Sleep Parameters - Number of Awakenings Withdrawal Period	2.19 Awakenings Standard Deviation 1.18	2.37 Awakenings Standard Deviation 0.80

SECONDARY outcome

Timeframe: Once during the withdrawal period

The Patient Global Impression is a 7-point scale which asks "How much has your sleep improved?" with the following anchors: no improvement, minimal improvement, slight improvement, moderate improvement, very good improvement, near complete improvement, and complete improvement.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=7 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Qualitative Evaluation of Sleep - Global Sleep Impression Complete improvement	0 Participants	1 Participants
Qualitative Evaluation of Sleep - Global Sleep Impression Moderate improvement	3 Participants	0 Participants
Qualitative Evaluation of Sleep - Global Sleep Impression Slight improvement	1 Participants	0 Participants
Qualitative Evaluation of Sleep - Global Sleep Impression Minimal improvement	0 Participants	2 Participants
Qualitative Evaluation of Sleep - Global Sleep Impression No improvement	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Every morning during the screening, treatment, and withdrawal periods

The subject rates the quality of her sleep on a scale of 0 through 10, where 0 is a very bad night of sleep and 10 is a very good night of sleep.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=8 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Qualitative Evaluation of Sleep - Quality of Sleep Screening Period	4.60 Units on a Scale Standard Deviation 1.32	5.32 Units on a Scale Standard Deviation 0.78
Qualitative Evaluation of Sleep - Quality of Sleep Treatment Period	5.47 Units on a Scale Standard Deviation 1.25	5.15 Units on a Scale Standard Deviation 0.93
Qualitative Evaluation of Sleep - Quality of Sleep Withdrawal Period	6.59 Units on a Scale Standard Deviation 2.06	5.47 Units on a Scale Standard Deviation 0.68

SECONDARY outcome

Timeframe: Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments

Population: Screening period: 12 patients with 6 treated with Placebo and 6 with Ramelteon. Treatment period: 11 patients with 4 treated with Placebo and 7 with Ramelteon. Withdrawal period: 8 patients with 4 treated with Placebo and 4 with Ramelteon.

The subject rates her fatigue on a scale of 0 through 10, where 0 is not a problem and 10 is as bad as possible.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=6 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Daytime Function - Fatigue Screening Period	3.06 Units on a Scale Standard Deviation 2.36	2.11 Units on a Scale Standard Deviation 1.70
Daytime Function - Fatigue Treatment Period	2.42 Units on a Scale Standard Deviation 0.79	4.07 Units on a Scale Standard Deviation 1.84
Daytime Function - Fatigue Withdrawal Period	3.38 Units on a Scale Standard Deviation 2.43	3.00 Units on a Scale Standard Deviation 2.45

SECONDARY outcome

Timeframe: Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments

Population: Screening period: 11 patients with 6 treated with Placebo and 5 with Ramelteon. Treatment period: 9 patients with 4 treated with Placebo and 5 with Ramelteon. Withdrawal period: 8 patients with 4 treated with Placebo and 4 with Ramelteon.

The subject rates 7 questions related to despair on a scale of 0 through 10 for each question, where 0 is not bad and 10 is as bad as possible. The scores of these 7 questions are combined and normalized, and used to describe despair.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=5 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Daytime Function - Despair Screening Period	47.07 Units on a Scale Standard Deviation 10.17	46.02 Units on a Scale Standard Deviation 6.92
Daytime Function - Despair Treatment Period	42.92 Units on a Scale Standard Deviation 0.00	45.15 Units on a Scale Standard Deviation 5.00
Daytime Function - Despair Withdrawal Period	49.38 Units on a Scale Standard Deviation 12.91	42.92 Units on a Scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments

The subject rates 4 questions related to distress on a scale of 0 through 10 for each question, where 0 is not bad and 10 is as bad as possible. The scores of these 4 questions are combined and normalized, and used to describe distress.

Outcome measures

Outcome measures
Measure	1 (Placebo) n=6 Participants Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=5 Participants Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Daytime Function - Distress Screening Period	42.91 Units on a Scale Standard Deviation 12.20	41.99 Units on a Scale Standard Deviation 9.07
Daytime Function - Distress Treatment Period	37.93 Units on a Scale Standard Deviation 0.00	39.86 Units on a Scale Standard Deviation 4.32
Daytime Function - Distress Withdrawal Period	45.40 Units on a Scale Standard Deviation 14.94	37.93 Units on a Scale Standard Deviation 0.00

Adverse Events

1 (Placebo)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

2 (Ramelteon)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Vice President of Scientific Affairs

Accelerated Community Oncology Research Network, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI must provide Sponsor an advance copy of any proposed publication whether in journals or in conferences or other public forum at least 60 days prior to any submission for publication or public presentation so that Sponsor may determine whether it contains any Confidential Information of Sponsor, and/or any discovery or invention is made.
Publication restrictions are in place

Restriction type: OTHER

Measure	1 (Placebo) n=7 participants at risk Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period.	2 (Ramelteon) n=9 participants at risk Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period.
Gastrointestinal disorders Dry mouth	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Gastrointestinal disorders Hematochezia	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	0.00% 0/9 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
General disorders Fatigue	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
General disorders Leg edema	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	0.00% 0/9 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
General disorders Pain on right side of chest	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	0.00% 0/9 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Infections and infestations Abscess on right hip	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Infections and infestations Sinus infection	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Infections and infestations Yeast infection	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Nervous system disorders Dizziness	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Nervous system disorders Headache	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	22.2% 2/9 • Number of events 2 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Respiratory, thoracic and mediastinal disorders Coughing	28.6% 2/7 • Number of events 2 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	0.00% 0/9 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Respiratory, thoracic and mediastinal disorders Respiratory virus	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	0.00% 0/9 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Respiratory, thoracic and mediastinal disorders Sore throat	14.3% 1/7 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	22.2% 2/9 • Number of events 2 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Gastrointestinal disorders Constipation	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Gastrointestinal disorders Nausea	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Infections and infestations Urinary tract infection	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.00% 0/7 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).	11.1% 1/9 • Number of events 1 • Adverse event data were collected beginning at Visit 2: Randomization Visit (Day 1) until Visit 4: Close-out Visit (Day 36). Systematic Assessment - subjects were assessed for adverse events at each study visit by either the research coordinator, treating physician, or other appropriate sub-investigator (such as a nurse practitioner or physician assistant).