Trial Outcomes & Findings for Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use (NCT NCT02785406)

NCT ID: NCT02785406

Last Updated: 2019-12-11

Results Overview

The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: day 0
• Results posted on: 2019-12-11

Participant Flow

Participant milestones

Measure	Suvorexant Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Overall Study STARTED	10	10
Overall Study Completed First Week	10	10
Overall Study Completed Second Week	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use

Baseline characteristics by cohort

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.	Total n=20 Participants Total of all reporting groups
Age, Continuous	44.7 years STANDARD_DEVIATION 6.7 • n=5 Participants	46.6 years STANDARD_DEVIATION 6.75 • n=7 Participants	45.65 years STANDARD_DEVIATION 6.62 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 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	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: day 0

Population: Data were not collected for 1 in the placebo arm.

The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=9 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Cue Reactivity as Assessed by the Attention Bias (AB) Task	0.524 score on a scale Standard Deviation 0.0846	0.519 score on a scale Standard Deviation 0.107

PRIMARY outcome

Timeframe: day 7

Population: Data were not collected for one in the suvorexant arm and one in the placebo arm.

The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

Outcome measures

Measure	Suvorexant n=9 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=9 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Cue Reactivity as Assessed by the Attention Bias (AB) Task	0.443 score on a scale Standard Deviation 0.0694	0.492 score on a scale Standard Deviation 0.149

PRIMARY outcome

Timeframe: day 14

Population: Data were not collected for one in the placebo arm.

The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=9 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Cue Reactivity as Assessed by the Attention Bias (AB) Task	0.488 score on a scale Standard Deviation 0.19	0.508 score on a scale Standard Deviation 0.0832

PRIMARY outcome

Timeframe: day 0

Population: Data were not collected for one in the suvorexant arm and 5 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=9 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=5 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	8.18 hours Standard Deviation 2.17	8.05 hours Standard Deviation 2.72

PRIMARY outcome

Timeframe: day 2

Population: Data were not collected for 2 in the suvorexant arm and 4 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=8 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=6 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	8.66 hours Standard Deviation 2.66	7.5 hours Standard Deviation 2.49

PRIMARY outcome

Timeframe: day 4

Population: Data were not collected for 4 in the suvorexant arm and 4 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=6 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=6 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	6.73 hours Standard Deviation 2.19	7.39 hours Standard Deviation 2.23

PRIMARY outcome

Timeframe: day 7

Population: Data were not collected for one in the suvorexant arm and 4 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=9 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=6 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	6.37 hours Standard Deviation 1.91	7.5 hours Standard Deviation 1.35

PRIMARY outcome

Timeframe: day 9

Population: Data were not collected for 2 in the suvorexant arm and 4 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=8 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=6 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	7.91 hours Standard Deviation 1.38	8.01 hours Standard Deviation 1.65

PRIMARY outcome

Timeframe: day 11

Population: Data were not collected for 4 in the suvorexant arm and 4 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=6 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=6 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	6.93 hours Standard Deviation 1.45	7.94 hours Standard Deviation 2.73

PRIMARY outcome

Timeframe: day 14

Population: Data were not collected for 3 in the suvorexant arm and 5 in the placebo arm.

Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

Outcome measures

Measure	Suvorexant n=7 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=5 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Total Sleep as Assessed by the Misfit Shine Device	6.57 hours Standard Deviation 1.96	7.56 hours Standard Deviation 0.95

PRIMARY outcome

Timeframe: day 0

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	4.4 score on a scale Standard Deviation 2.84	3.8 score on a scale Standard Deviation 3.77

PRIMARY outcome

Timeframe: day 2

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	3.8 score on a scale Standard Deviation 2.44	2.5 score on a scale Standard Deviation 2.84

PRIMARY outcome

Timeframe: day 4

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	2.7 score on a scale Standard Deviation 2.31	3.1 score on a scale Standard Deviation 4.28

PRIMARY outcome

Timeframe: day 7

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	1.7 score on a scale Standard Deviation 1.7	2.7 score on a scale Standard Deviation 3.3

PRIMARY outcome

Timeframe: day 9

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	1.9 score on a scale Standard Deviation 2.18	2.3 score on a scale Standard Deviation 3.3

PRIMARY outcome

Timeframe: day 11

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	2 score on a scale Standard Deviation 2.31	2.4 score on a scale Standard Deviation 3.24

PRIMARY outcome

Timeframe: day 14

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale	2.8 score on a scale Standard Deviation 2.66	2.3 score on a scale Standard Deviation 4.11

PRIMARY outcome

Timeframe: day 0

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale.	2.6 score on a scale Standard Deviation 1.84	2.3 score on a scale Standard Deviation 2

PRIMARY outcome

Timeframe: day 2

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale	1.9 score on a scale Standard Deviation 2.02	2.1 score on a scale Standard Deviation 2.28

PRIMARY outcome

Timeframe: day 4

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale	1.5 score on a scale Standard Deviation 2.12	1.4 score on a scale Standard Deviation 1.65

PRIMARY outcome

Timeframe: day 7

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale	1.5 score on a scale Standard Deviation 2.42	1.2 score on a scale Standard Deviation 1.48

PRIMARY outcome

Timeframe: day 9

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale	1.4 score on a scale Standard Deviation 2.32	0.9 score on a scale Standard Deviation 1.1

PRIMARY outcome

Timeframe: day 11

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale	1.4 score on a scale Standard Deviation 1.9	0.8 score on a scale Standard Deviation 1.03

PRIMARY outcome

Timeframe: day 14

DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Anxiety as Assessed by the DASS21 Self-report Questionnaire	2.2 score on a scale Standard Deviation 2.49	1.1 score on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: day 0, day 7, and day 14

The Cocaine Craving Questionnaire (CCQ) Brief is a self-report, 14-item measure with five conceptual domains: Desire to Use, Intention to Use, Anticipation of Positive Outcome, Anticipation of Relief from Dysphoria, and Lack of Control over use. The measure is well validated and has been used in multiple studies of CUD. Total score ranges from 1 to 7. A higher score indicates a worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief day 0	3.61 score on a scale Standard Deviation 1.24	2.7 score on a scale Standard Deviation 1.26
Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief day 7	3.01 score on a scale Standard Deviation 1.3	2.8 score on a scale Standard Deviation 1.02
Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief day 14	2.92 score on a scale Standard Deviation 1.47	2.48 score on a scale Standard Deviation 0.98

SECONDARY outcome

Timeframe: day 0, day 2, day 4, day 7, day 9, day 11, and day 14

Population: Data were not collected for days 2, 4, 9, and 11. For days 0, 7, and 14, where number analyzed is less than 10, data were not collected for the number that are not reported.

The Pittsburg Sleep Quality Index (PSQI) is an 18-item self-report measure of sleep, providing a well-validated and reliable measure of sleep quality, latency, duration, duration efficiency, and disturbance, and an overall summary. The overall summary score will be reported for this measure. The PSQI has been used in several studies of individuals with SUD, including cocaine. Total score ranges from 0-21, with a higher score indicating worse outcome.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) day 0	7.5 score on a scale Standard Deviation 2.46	7 score on a scale Standard Deviation 2.36
Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) day 7	9.38 score on a scale Standard Deviation 4.24	6.6 score on a scale Standard Deviation 2.91
Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) day 14	8.2 score on a scale Standard Deviation 3.19	4.89 score on a scale Standard Deviation 1.76

SECONDARY outcome

Timeframe: day 0, day 7, and day 14

Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure day 0, immediately before CPT	125 millimeters of mercury (mmHg) Standard Deviation 12.9	120 millimeters of mercury (mmHg) Standard Deviation 17.4
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure day 7, immediately before CPT	126 millimeters of mercury (mmHg) Standard Deviation 10.3	125 millimeters of mercury (mmHg) Standard Deviation 16.1
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure day 14, immediately before CPT	128 millimeters of mercury (mmHg) Standard Deviation 17.7	121 millimeters of mercury (mmHg) Standard Deviation 16.6
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure day 0, immediately after CPT	123 millimeters of mercury (mmHg) Standard Deviation 12.3	113 millimeters of mercury (mmHg) Standard Deviation 13.5
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure day 7, immediately after CPT	122 millimeters of mercury (mmHg) Standard Deviation 12.2	132 millimeters of mercury (mmHg) Standard Deviation 19.3
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure day 14, immediately after CPT	120 millimeters of mercury (mmHg) Standard Deviation 15.8	120 millimeters of mercury (mmHg) Standard Deviation 20

SECONDARY outcome

Timeframe: day 0, day 7, and day 14

Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure day 0, immediately before CPT	84.6 millimeters of mercury (mmHg) Standard Deviation 9.43	80.7 millimeters of mercury (mmHg) Standard Deviation 17.4
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure day 7, immediately before CPT	84.8 millimeters of mercury (mmHg) Standard Deviation 10.5	83.6 millimeters of mercury (mmHg) Standard Deviation 12
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure day 14, immediately before CPT	85.4 millimeters of mercury (mmHg) Standard Deviation 12.9	81.1 millimeters of mercury (mmHg) Standard Deviation 10
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure day 0, immediately after CPT	82 millimeters of mercury (mmHg) Standard Deviation 8.51	72.3 millimeters of mercury (mmHg) Standard Deviation 9.1
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure day 7, immediately after CPT	82.6 millimeters of mercury (mmHg) Standard Deviation 9.34	87.2 millimeters of mercury (mmHg) Standard Deviation 13.1
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure day 14, immediately after CPT	76.3 millimeters of mercury (mmHg) Standard Deviation 19.3	80.2 millimeters of mercury (mmHg) Standard Deviation 12.4

SECONDARY outcome

Timeframe: day 0, day 7, and day 14

Population: Where number analyzed is less than 10, data were not collected for the number that are not reported.

Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) day 0, immediately before CPT	553 pg/mL Standard Deviation 291	1269 pg/mL Standard Deviation 2070
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) day 7, immediately before CPT	1108 pg/mL Standard Deviation 690	957 pg/mL Standard Deviation 1211
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) day 14, immediately before CPT	532 pg/mL Standard Deviation 522	629 pg/mL Standard Deviation 391
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) day 0, immediately after CPT	582 pg/mL Standard Deviation 448	894 pg/mL Standard Deviation 377
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) day 7, immediately after CPT	873 pg/mL Standard Deviation 904	1280 pg/mL Standard Deviation 2063
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) day 14, immediately after CPT	589 pg/mL Standard Deviation 286	1120 pg/mL Standard Deviation 770

SECONDARY outcome

Timeframe: day 0, day 2, day 4, day 7, day 9, day 11, and day 14

Score provided is the total score (0 to 300) across three items that are each on a 0-100 scale. A higher score indicates greater stress.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 0	192 units on a scale Standard Deviation 44.1	138 units on a scale Standard Deviation 63
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 2	168 units on a scale Standard Deviation 54.8	127 units on a scale Standard Deviation 52.6
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 4	151 units on a scale Standard Deviation 80.5	124 units on a scale Standard Deviation 53.2
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 7	128 units on a scale Standard Deviation 50.1	134 units on a scale Standard Deviation 75.4
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 9	145 units on a scale Standard Deviation 45.9	118 units on a scale Standard Deviation 66.3
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 11	145 units on a scale Standard Deviation 54.9	142 units on a scale Standard Deviation 66.2
Stress as Assessed by a Visual Analog Scale (VAS) for Stress day 14	142 units on a scale Standard Deviation 79.4	119 units on a scale Standard Deviation 76.4

SECONDARY outcome

Timeframe: day 2, day 4, day 7, day 9, day 11, and day 14

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles day 2	91.9 percent medication compliance Standard Deviation 0.302	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles day 4	81.8 percent medication compliance Standard Deviation 0.405	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles day 7	81.8 percent medication compliance Standard Deviation 0.405	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles day 9	81.8 percent medication compliance Standard Deviation 0.405	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles day 11	100 percent medication compliance Standard Deviation 0	75 percent medication compliance Standard Deviation 0.463
Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles day 14	81.8 percent medication compliance Standard Deviation 0.405	87.5 percent medication compliance Standard Deviation 0.354

SECONDARY outcome

Timeframe: day 2, day 4, day 7, day 9, day 11, and day 14

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Percent Medication Compliance as Assessed by Pill Counts day 2	95.5 percent medication compliance Standard Deviation 0.151	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Pill Counts day 4	95 percent medication compliance Standard Deviation 0.158	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Pill Counts day 7	100 percent medication compliance Standard Deviation 0	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Pill Counts day 9	100 percent medication compliance Standard Deviation 0	88.9 percent medication compliance Standard Deviation 0.333
Percent Medication Compliance as Assessed by Pill Counts day 11	90 percent medication compliance Standard Deviation 0.316	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Pill Counts day 14	100 percent medication compliance Standard Deviation 0	100 percent medication compliance Standard Deviation 0

SECONDARY outcome

Timeframe: day 2, day 4, day 7, day 9, day 11, and day 14

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples day 2	100 percent medication compliance Standard Deviation 0	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples day 4	100 percent medication compliance Standard Deviation 0	89 percent medication compliance Standard Deviation 0.333
Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples day 7	100 percent medication compliance Standard Deviation 0	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples day 9	100 percent medication compliance Standard Deviation 0	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples day 11	90 percent medication compliance Standard Deviation 0.316	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples day 14	100 percent medication compliance Standard Deviation 0	100 percent medication compliance Standard Deviation 0

SECONDARY outcome

Timeframe: day 2, day 4, day 7, day 9, day 11, and day 14

Text-based reminders to take the medication will be enabled via using a HIPAA secure texting service (Talksoft ©), used broadly in medical settings. Participants will be prompted each night at 10 PM to take their medication, and instructed to text back "yes" when they have taken their medication.

Outcome measures

Measure	Suvorexant n=10 Participants Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Placebo n=10 Participants Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Percent Medication Compliance as Assessed by Text Reminders and Replies day 2	55.6 percent medication compliance Standard Deviation 0.527	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Text Reminders and Replies day 4	55.6 percent medication compliance Standard Deviation 0.527	87.5 percent medication compliance Standard Deviation 0.354
Percent Medication Compliance as Assessed by Text Reminders and Replies day 7	70 percent medication compliance Standard Deviation 0.483	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Text Reminders and Replies day 9	70 percent medication compliance Standard Deviation 0.483	100 percent medication compliance Standard Deviation 0
Percent Medication Compliance as Assessed by Text Reminders and Replies day 11	90 percent medication compliance Standard Deviation 0.316	75 percent medication compliance Standard Deviation 0.463
Percent Medication Compliance as Assessed by Text Reminders and Replies day 14	87.5 percent medication compliance Standard Deviation 0.354	75 percent medication compliance Standard Deviation 0.463

Adverse Events

Suvorexant

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Scott Lane

The University of Texas Health Science Center at Houston

Phone: 713-486-2535

Email: Scott.D.Lane@uth.tmc.edu

Results disclosure agreements

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