Trial Outcomes & Findings for Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal (NCT NCT04070157)

NCT ID: NCT04070157

Last Updated: 2024-10-21

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

Day 1 through Day 28

Results posted on

2024-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	Lofexidine Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Overall Study STARTED	1	3
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Day 1 through Day 28

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Number of Treatment Emergent AEs and SAEs Adverse Events	5 participants	—	—	0 participants
Number of Treatment Emergent AEs and SAEs Serious Adverse Events	0 participants	—	—	0 participants

PRIMARY outcome

Timeframe: Day 1 through Day 28

Population: There were zero Treatment Emergent AE's.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Number and Percent of Subjects Reporting TEAEs Resulting in Study Drug Discontinuation	1 Participants	—	—	0 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 28

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Percentage of Subjects With Treatment-emergent Elevated Liver Function Tests	0 Participants	—	—	0 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 28

Population: All responses were "No".

The C-SSRS measures both suicidal ideation and suicidal behavior. The Screener contains "yes" or "no" questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide. A significant risk of suicide is defined as a "yes" in answer to: a) questions 4 or 5 on the suicidal ideation section, or b) any questions on any item in the suicidal behavior section. This must be reported as an SAE and followed up accordingly. Additionally, if a subject responds "yes" to any of the suicidal ideation questions 1 to 3, the Investigator should apply clinical judgment to determine the need for reporting as an AE or SAE and the need for any referral.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Percentage of Subjects Identified as Suicide Risk With Columbia Suicide Severity Rating Scale	0 % of subjects with suicide risk	—	—	0 % of subjects with suicide risk

PRIMARY outcome

Timeframe: Baseline to Days 1, 2, 3, 7, 8, 14, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28

Population: A pause patient in the Placebo group had their End of Study on Visit Day 37. All other participants completed their EOS by Day 28. Orthostatic vital signs only collected in clinic.

Orthostatic vital signs were measured in-clinic only. When the subject is at home, only resting vital signs will be collected. Orthostatic vital signs will be measured first after the subject has been sitting for at least 5 minutes and then after the subject has been standing for at least 3 minutes. Resting vital signs only will be measured at home and will be measured after the subject has been sitting quietly for at least 5 minutes.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=1 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: n=3 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Blood Pressure Day 1: Diastolic BP	0 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	-0.3 mmHg Standard Deviation 3.06	-0.7 mmHg Standard Deviation 3.21	-2 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 1: Systolic BP	0 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	1.7 mmHg Standard Deviation 2.31	-0.3 mmHg Standard Deviation 1.53	-6 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 2: Diastolic BP	—	3 mmHg Standard Deviation 5.66	—	-7 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 2: Systolic BP	—	7 mmHg Standard Deviation 9.9	—	-25 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 3: Diastolic BP	-9 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	1.5 mmHg Standard Deviation 3.87	5 mmHg Standard Deviation 6	-16 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 3: Systolic BP	-44 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	6.5 mmHg Standard Deviation 7.72	6 mmHg Standard Deviation 7.94	-52 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 7: Diastolic BP	—	7 mmHg Standard Deviation 8.72	—	-16 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 7: Systolic BP	—	6 mmHg Standard Deviation 7	—	-50 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 8: Diastolic BP	-8 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	3.3 mmHg Standard Deviation 9.45	5.3 mmHg Standard Deviation 5.86	-10 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 8: Systolic BP	-36 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	4 mmHg Standard Deviation 11	3 mmHg Standard Deviation 11	-44 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 14: Diastolic BP	—	1.7 mmHg Standard Deviation 10.5	—	-8 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 14: Systolic BP	—	4.7 mmHg Standard Deviation 10.02	—	-42 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 15: Diastolic BP	-4 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	1 mmHg Standard Deviation 7.81	3.3 mmHg Standard Deviation 7.77	-10 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 15: Systolic BP	-40 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	10.7 mmHg Standard Deviation 16.07	4.3 mmHg Standard Deviation 13.01	-32 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 18: Systolic BP	—	14.3 mmHg Standard Deviation 0.58	—	—
Change in Blood Pressure Day 19: Diastolic BP	—	6.3 mmHg Standard Deviation 4.5	—	—
Change in Blood Pressure Day 19: Systolic BP	—	11 mmHg Standard Deviation 6.22	—	—
Change in Blood Pressure Day 20: Diastolic BP	—	1.8 mmHg Standard Deviation 5.91	—	—
Change in Blood Pressure Day 20: Systolic BP	—	4.3 mmHg Standard Deviation 7.68	—	—
Change in Blood Pressure Day 21: Diastolic BP	—	8.5 mmHg Standard Deviation 3.42	—	—
Change in Blood Pressure Day 21: Systolic BP	—	11.8 mmHg Standard Deviation 11.12	—	—
Change in Blood Pressure Day 22: Diastolic BP	-8 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	4.3 mmHg Standard Deviation 3.72	10 mmHg Standard Deviation 1.41	-16 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 22: Systolic BP	-34 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	9.7 mmHg Standard Deviation 16.02	16 mmHg Standard Deviation 1.41	-25 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 23: Diastolic BP	—	3.5 mmHg Standard Deviation 5.45	—	-3.5 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 23: Systolic BP	—	11.5 mmHg Standard Deviation 12.23	—	-19 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 24: Diastolic BP	—	6.3 mmHg Standard Deviation 4.5	—	-1.5 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 24: Systolic BP	—	9.5 mmHg Standard Deviation 6.61	—	-23.5 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 25: Diastolic BP	—	4.7 mmHg Standard Deviation 3.56	—	—
Change in Blood Pressure Day 27: Systolic BP	—	7.7 mmHg Standard Deviation 8.16	—	—
Change in Blood Pressure Day 28: Diastolic BP	—	11 mmHg Standard Deviation 7.07	7.5 mmHg Standard Deviation 4.95	—
Change in Blood Pressure Day 28: Systolic BP	—	22 mmHg Standard Deviation 7.07	15.5 mmHg Standard Deviation 14.85	—
Change in Blood Pressure Day 29: Diastolic BP	—	-0.5 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—
Change in Blood Pressure Day 29: Systolic BP	—	18 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—
Change in Blood Pressure Day 30: Diastolic BP	—	-1.5 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—
Change in Blood Pressure Day 30: Systolic BP	—	8 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—
Change in Blood Pressure Day 37: Diastolic BP	—	0 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	3 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—
Change in Blood Pressure Day 37: Systolic BP	—	-5 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	-5 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—
Change in Blood Pressure Day 18: Diastolic BP	—	10.7 mmHg Standard Deviation 6.35	—	—
Change in Blood Pressure Day 25: Systolic BP	—	8.5 mmHg Standard Deviation 9.57	—	—
Change in Blood Pressure Day 26: Diastolic BP	—	9.3 mmHg Standard Deviation 7.46	—	1.5 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 26: Systolic BP	—	8.5 mmHg Standard Deviation 19.28	—	-14 mmHg Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Blood Pressure Day 27: Diastolic BP	—	4.8 mmHg Standard Deviation 4.67	—	—
Change in Blood Pressure Day 34: Diastolic BP	—	0.5 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—
Change in Blood Pressure Day 34: Systolic BP	—	12.5 mmHg Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—

PRIMARY outcome

Timeframe: Baseline to Days 1, 2, 3, 7, 8, 14, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28

Population: A pause patient in the Placebo group had their End of Study on Visit Day 37. All other participants completed their EOS by Day 28. Orthostatic vital signs only collected in clinic.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=1 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: n=3 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Pulse Day 1	0 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	-5 bpm Standard Deviation 2.65	-0.3 bpm Standard Deviation 3.21	1 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 3	-5 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	-7.3 bpm Standard Deviation 2.63	-5.3 bpm Standard Deviation 0.58	-4 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 7	—	-2 bpm Standard Deviation 9.54	—	0 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 8	-4 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	-1 bpm Standard Deviation 3.46	-0.7 bpm Standard Deviation 0.58	-2 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 14	—	-1.7 bpm Standard Deviation 7.09	—	-1 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 15	0 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	-11 bpm Standard Deviation 8.19	-3 bpm Standard Deviation 3.46	-2 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 18	—	1.7 bpm Standard Deviation 2.89	—	—
Change in Pulse Day 19	—	-2.8 bpm Standard Deviation 4.03	—	—
Change in Pulse Day 20	—	-8.8 bpm Standard Deviation 5.12	—	—
Change in Pulse Day 21	—	-1.8 bpm Standard Deviation 8.54	—	—
Change in Pulse Day 22	-5 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.	-6 bpm Standard Deviation 4.1	-7 bpm Standard Deviation 2.83	-4 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 25	—	-0.8 bpm Standard Deviation 7.78	—	—
Change in Pulse Day 26	—	-9 bpm Standard Deviation 4.97	—	0.5 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 27	—	-5.5 bpm Standard Deviation 7.31	—	—
Change in Pulse Day 28	—	-7.5 bpm Standard Deviation 3.54	-7 bpm Standard Deviation 11.31	—
Change in Pulse Day 2	—	-9 bpm Standard Deviation 4.24	—	-2 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 23	—	-4 bpm Standard Deviation 11.8	—	0.5 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 24	—	-6.5 bpm Standard Deviation 4.2	—	-1 bpm Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Pulse Day 29	—	3.5 bpm Standard Deviation NA Only 1 participant remaining in Placebo group, standard deviation not possible.	—	—
Change in Pulse Day 30	—	1.5 bpm Standard Deviation NA Only 1 participant remaining in Placebo group, standard deviation not possible.	—	—
Change in Pulse Day 34	—	2.5 bpm Standard Deviation NA Only 1 participant remaining in Placebo group, standard deviation not possible.	—	—
Change in Pulse Day 37	—	-13 bpm Standard Deviation NA Only 1 participant remaining in Placebo group, standard deviation not possible.	-8 bpm Standard Deviation NA Only 1 participant remaining in Placebo group, standard deviation not possible.	—

SECONDARY outcome

Timeframe: Day 1 through Day 28

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Percentage of Subjects Who Successfully Complete Each Scheduled Dose Reduction and the Opioid Taper to Complete Opioid Discontinuation	2 Participants	—	—	0 Participants

SECONDARY outcome

Timeframe: Day 1 (pre-1st dose) to Days 3, 8, 15, 22 and 28

The COWS is a clinician-administered instrument that rates 11 common opioid withdrawal signs and symptoms. These include: resting pulse rate; sweating; restlessness; pupil size; bone or joint aches; runny nose or tearing; gastrointestinal upset; tremor; yawning; anxiety or irritability; and gooseflesh skin. Lower total scores indicate a more positive clinical outcome. Score: 5-12 = mild; 13-24 = moderately severe; more than 36 = severe withdrawal. Scores range from a minimum of 0 to a maximum of 48.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Clinical Opiate Withdrawal Scale (COWS) Day 8	-1 score on a scale Standard Deviation 2	—	—	3 score on a scale
Change in Clinical Opiate Withdrawal Scale (COWS) Day 15	-1.3 score on a scale Standard Deviation 0.58	—	—	4 score on a scale
Change in Clinical Opiate Withdrawal Scale (COWS) End of Study	-2.3 score on a scale Standard Deviation 0.58	—	—	-1 score on a scale
Change in Clinical Opiate Withdrawal Scale (COWS) Day 3	-0.7 score on a scale Standard Deviation 0.58	—	—	2 score on a scale
Change in Clinical Opiate Withdrawal Scale (COWS) Day 22	-2.5 score on a scale Standard Deviation 0.71	—	—	-1 score on a scale

SECONDARY outcome

Timeframe: Day 1 (pre-1st dose) to Days 1 (at bedtime), 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28

Population: A pause patient in the Placebo group had their End of Study on Visit Day 37. All other participants completed their EOS by Day 28. All remaining blank fields had no data collection.

The SOWS-Gossop scale assesses subjective symptoms of opioid withdrawal. It is a subject-rated scale consisting of 10 items that are scored on a 4-point scale of 0 = none, 1 = mild, 2 = moderate, and 3 = severe (minimum score of 0, maximum score of 30). The overall score is the simple sum of the 10 item scores. Lower observed values in SOWS-Gossop scores indicate a more positive clinical outcome.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 2	-0.5 score on a scale Standard Deviation 3	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 3	-2.2 score on a scale Standard Deviation 3.56	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 4	-0.7 score on a scale Standard Deviation 5.03	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 5	-0.3 score on a scale Standard Deviation 5.51	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 6	0.3 score on a scale Standard Deviation 5.03	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 7	-2.5 score on a scale Standard Deviation 3.54	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 8	-1.4 score on a scale Standard Deviation 4.72	—	—	1.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 9	2 score on a scale Standard Deviation 6	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 10	-4.5 score on a scale Standard Deviation 0.71	—	—	4 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 11	-0.3 score on a scale Standard Deviation 6.35	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 12	-4.5 score on a scale Standard Deviation 0.71	—	—	2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 13	-1 score on a scale Standard Deviation 6.08	—	—	4 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 14	-1 score on a scale Standard Deviation 6.08	—	—	5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 15	-4.3 score on a scale Standard Deviation 0.96	—	—	2.7 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 16	1.5 score on a scale Standard Deviation 6.45	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 17	-4 score on a scale Standard Deviation 1.41	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 18	-4 score on a scale Standard Deviation 1.41	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 19	-4 score on a scale Standard Deviation 1.41	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 22	-3.8 score on a scale Standard Deviation 2.49	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 23	-2.7 score on a scale Standard Deviation 2.52	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 24	-3 score on a scale Standard Deviation 3	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 25	-4.5 score on a scale Standard Deviation 2.12	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 27	-4 score on a scale Standard Deviation 1.41	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 28	-3.8 score on a scale Standard Deviation 2.87	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 20	-4 score on a scale Standard Deviation 1.41	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 21	-4 score on a scale Standard Deviation 1.41	—	—	—
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G) Day 26	-3 score on a scale Standard Deviation 3	—	—	—

SECONDARY outcome

Timeframe: Day 1 (pre-1st dose) to Days 1 (at bedtime), 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28

Population: A pause patient in the Placebo group had their End of Study on Visit Day 37. All other participants completed their EOS by Day 28. All remaining blank fields had no data collection.

The SOWS-H scale assesses subjective symptoms of opioid withdrawal. It is a subject-rated scale consisting of 19 items that are scored on a 5-point scale of 0 = not at all, 1 = a little, 2 = moderately, 3 = quite a bit, and 4 = extremely. The overall score is the simple sum of the 19 item scores. Lower observed values in SOWS-H scores indicate a more positive clinical outcome.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 2	0.3 score on a scale Standard Deviation 3.77	—	—	-4 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 3	-1 score on a scale Standard Deviation 4.3	—	—	-5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 4	2.3 score on a scale Standard Deviation 5.51	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 5	3 score on a scale Standard Deviation 6.24	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 6	3.3 score on a scale Standard Deviation 8.02	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 7	0 score on a scale Standard Deviation 5.66	—	—	-4 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 8	1.8 score on a scale Standard Deviation 6.3	—	—	-2.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 10	-1.5 score on a scale Standard Deviation 3.54	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 11	0.7 score on a scale Standard Deviation 6.35	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 12	-4 score on a scale Standard Deviation 0	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 13	-0.3 score on a scale Standard Deviation 8.14	—	—	2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 14	0.7 score on a scale Standard Deviation 8.96	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 15	-3.5 score on a scale Standard Deviation 1.29	—	—	0.7 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 16	4.3 score on a scale Standard Deviation 9	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 17	-4 score on a scale Standard Deviation 1.41	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 18	-3 score on a scale Standard Deviation 0	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 19	-3 score on a scale Standard Deviation 0	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 20	-3.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 21	-4 score on a scale Standard Deviation 0	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 24	-2.3 score on a scale Standard Deviation 2.89	—	—	-5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 25	-4.5 score on a scale Standard Deviation 0.71	—	—	-5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 26	-3.3 score on a scale Standard Deviation 2.52	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 27	-4 score on a scale Standard Deviation 0	—	—	-6 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 9	3.5 score on a scale Standard Deviation 7.59	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 22	-2.8 score on a scale Standard Deviation 1.3	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 23	-3.3 score on a scale Standard Deviation 2.08	—	—	—
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H) Day 28	-3.8 score on a scale Standard Deviation 1.89	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.

SECONDARY outcome

Timeframe: Each scheduled evaluation (Study Visits 2, 3, 4, 5, EOS)

MCGI-R includes 2 items: A 7-point scale that allows clinicians to rate the severity of a subject's opiate withdrawal symptoms. A 4-point scale that allows clinicians to rate the degree of a subject's side effects from study drug. SEVERITY OF ILLNESS: 1. = No at all ill 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects SIDE EFFECTS INDEX: 1. = None, study drug is producing no side effects 2. = Do not significantly interfere with subject's functioning 3. = Significantly interferes with subject's functioning 4. = Outweighs therapeutic effect

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Modified Clinical Global Impression - Rater Version (MCGI-R) Average Score Visit 2	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.
Modified Clinical Global Impression - Rater Version (MCGI-R) Average Score Visit 3	1.33 score on a scale Standard Deviation 0.471	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.	1.33 score on a scale Standard Deviation 0.471	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.
Modified Clinical Global Impression - Rater Version (MCGI-R) Average Score Visit 4	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.
Modified Clinical Global Impression - Rater Version (MCGI-R) Average Score Visit 5	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.
Modified Clinical Global Impression - Rater Version (MCGI-R) Average Score EOS	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale Standard Deviation NA Only 1 participant. Standard deviation not possible.

SECONDARY outcome

Timeframe: Each scheduled evaluation (Day 1 through Day 28)

Population: No data collection for field with 0 participants.

Includes: A 7-point scale for subjects to rate the severity of opiate withdrawal symptoms. A 4-point scale for subjects to rate the degree of side effects from their study drug. SEVERITY OF OPIATE WITHDRAWAL: 1. = No opiate withdrawal symptoms 2. = On the border between no to mild opiate withdrawal symptoms 3. = Mild opiate withdrawal symptoms 4. = Moderate opiate withdrawal symptoms 5. = Marked opiate withdrawal symptoms 6. = Severe opiate withdrawal symptoms 7. = The most severe opiate withdrawal symptoms that I have ever had SIDE EFFECTS INDEX (Scale B): 1. = None. The study drug has no side effects 2. = The study drug has slight side effects, but it does NOT significantly interfere with my day to day activities 3. = The study drug has moderate side effects, and it DOES significantly interfere with my day to day activities 4. = The study drug has severe side effects, and these side effects are greater than the relief from opiate withdrawal symptoms that it provides

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 14	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale	1.66 score on a scale Standard Deviation 0.471	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 2	1.33 score on a scale Standard Deviation 0.471	1 score on a scale	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 3	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 4	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 5	1.66 score on a scale Standard Deviation 0.471	1 score on a scale	1.66 score on a scale Standard Deviation 0.471	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 8	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 10	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale	1.66 score on a scale Standard Deviation 0.471	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 11	1.66 score on a scale Standard Deviation 0.471	—	1.66 score on a scale Standard Deviation 0.471	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 12	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 13	1.66 score on a scale Standard Deviation 0.471	1 score on a scale	1.66 score on a scale Standard Deviation 0.471	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 15	1.66 score on a scale Standard Deviation 0.471	1 score on a scale	1.66 score on a scale Standard Deviation 0.471	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 16	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—	1.66 score on a scale Standard Deviation 0.471	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 19	1.5 score on a scale Standard Deviation 0.5	—	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 23	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 24	1.33 score on a scale Standard Deviation 0.471	1 score on a scale	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 25	1.5 score on a scale Standard Deviation 0.5	1 score on a scale	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 26	1.33 score on a scale Standard Deviation 0.471	—	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 6	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—	1.66 score on a scale Standard Deviation 0.471	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 7	1.66 score on a scale Standard Deviation 0.471	1 score on a scale	1.66 score on a scale Standard Deviation 0.471	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 9	1.66 score on a scale Standard Deviation 0.471	—	1.66 score on a scale Standard Deviation 0.471	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 17	1.5 score on a scale Standard Deviation 0.5	—	1.5 score on a scale Standard Deviation 0.5	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 18	1.5 score on a scale Standard Deviation 0.5	—	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 20	1.5 score on a scale Standard Deviation 0.5	—	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 21	1.5 score on a scale Standard Deviation 0.5	—	2 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 22	1.33 score on a scale Standard Deviation 0.471	—	1.66 score on a scale Standard Deviation 0.471	—
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 27	1.5 score on a scale Standard Deviation 0.5	1 score on a scale	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	1 score on a scale
Modified Clinical Global Impression - Subject Version (MCGI-S) Day 28	1.33 score on a scale Standard Deviation 0.471	1 score on a scale	1 score on a scale Standard Deviation NA Standard deviation not possible as values were the same for all participants.	—

SECONDARY outcome

Timeframe: Day 1 through Day 28

Study day of participant discontinuation.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=1 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: n=1 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Time to Study Drug Discontinuation	20 Days to study discontinuation	22 Days to study discontinuation	24 Days to study discontinuation	21 Days to study discontinuation

SECONDARY outcome

Timeframe: Day 1 through Day 28

Population: No data collection for field with 0 participants.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=1 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: n=1 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Number of Non-opioid Concomitant Medications for Withdrawal Symptoms Used by Study Day Day 1-15:	1 Number concomitant medication	1 Number concomitant medication	1 Number concomitant medication	0 Number concomitant medication
Number of Non-opioid Concomitant Medications for Withdrawal Symptoms Used by Study Day Day 16- Day 28:	1 Number concomitant medication	1 Number concomitant medication	—	1 Number concomitant medication

SECONDARY outcome

Timeframe: Change from Baseline to EOS

The EQ-5D-5L is an instrument that evaluates preference for health status through 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each of which are rated on 5 levels of severity. Each dimension ranges from a minimum of "0 - I have no problems or I am not" to a maximum of "5 - I am unable to or I am extremely". The dimensions are averaged together for a single score and the change in average score from baseline is recorded.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale	-0.13 score on a scale Standard Deviation 0.462	—	—	-0.40 score on a scale Standard Deviation NA No standard deviation since only 1 participant analyzed

SECONDARY outcome

Timeframe: Change from baseline to End of Study, up to 55 days

The SF-36 consists of 36 questions that measure various aspects of physical and mental well-being. Precoded values are recorded for each question ranging from 0-100, with a high score defined as a more favorable health status. The items are then averaged together to create the 8 scale scores which are averaged together to create a scale. The final value reported is the average change in the averaged scale scores from baseline to end of study.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Short Form Health Survey (SF-36) Scale	-1.7 score on a scale Standard Deviation 2.52	—	—	-5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.

SECONDARY outcome

Timeframe: Change from baseline to Days 15 and End of Study, up to 55 days

The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated are: severity of sleep onset, sleep maintenance and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep difficulties. A 5-point Likert scale is used to rate each item on a scale 0 to 4 for each of the 7 items, yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Insomnia Severity Index (ISI) Day 15	-4 score on a scale Standard Deviation 3	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Insomnia Severity Index (ISI) EOS	1 score on a scale Standard Deviation 1.73	—	—	-9 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.

SECONDARY outcome

Timeframe: Change from End of Study to Baseline, up to 55 days

The HADS is a self-reported screening tool for anxiety and depression in nonpsychiatric clinical populations. Responses are based on the relative frequency of symptoms over the preceding week. The scale consists of 14 items, with a subscale of 7 questions for anxiety and 7 questions for depression. Patients rate each item in the subscales on a 4-point scale ranging from 0 (absence) to 3 (extreme presence). Possible scores range from 0 to 21 for each subscale. An analysis of scores on the 2 subscales supported the differentiation of each mood state into 4 ranges: non-cases (scores 0 to 7), mild cases (scores 8 to 10), moderate cases (scores 11 to 15), and severe cases (scores 16 or higher), with lower values being favorable. The subscales are then combined for a total score ranging from 0 to 42. Higher scores indicate greater levels of anxiety or depression. The value reported is the average change from baseline to End of Study.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Hospital Anxiety and Depression Scale (HADS)	-2.3 score on a scale Standard Deviation 3.51	—	—	-2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.

SECONDARY outcome

Timeframe: Baseline through Follow-up (assessed daily)

Population: No data collection for field with 0 participants.

A subject selects a whole number (0 to 10) that best indicates the intensity of his/her pain. The format consists of a horizontal line which is anchored by terms defining pain levels where 0 represents no pain and 10 represents worst pain imaginable.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 3	-1.4 score on a scale Standard Deviation 1.82	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 4	-0.7 score on a scale Standard Deviation 1.53	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 5	-1.3 score on a scale Standard Deviation 1.15	—	—	-2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 7	-0.7 score on a scale Standard Deviation 1.53	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 8	-0.8 score on a scale Standard Deviation 2.63	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 9	-1 score on a scale Standard Deviation 0.82	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 10	-0.5 score on a scale Standard Deviation 2.12	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 15	-0.8 score on a scale Standard Deviation 1.5	—	—	-0.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 16	-1 score on a scale Standard Deviation 0	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 17	-1 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 20	0 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 21	-1.5 score on a scale Standard Deviation 2.12	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 22	-1.2 score on a scale Standard Deviation 1.83	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 24	-0.7 score on a scale Standard Deviation 1.53	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 25	-0.5 score on a scale Standard Deviation 2.12	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 27	0 score on a scale Standard Deviation 2.83	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 28	-0.5 score on a scale Standard Deviation 1.73	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 29	0.7 score on a scale Standard Deviation 1.53	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 31	-0.7 score on a scale Standard Deviation 1.53	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 32	-1.5 score on a scale Standard Deviation 0.71	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 42	-1 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 43	-1 score on a scale Standard Deviation 1.41	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 45	-0.5 score on a scale Standard Deviation 0.71	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 46	-0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 47	0 score on a scale Standard Deviation 1.41	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 48	0 score on a scale Standard Deviation 1.41	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 49	-0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 50	-0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 51	0 score on a scale Standard Deviation 1.41	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 1	-0.3 score on a scale Standard Deviation 0.82	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 2	-1.5 score on a scale Standard Deviation 1	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 6	-1 score on a scale Standard Deviation 1	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 11	-0.3 score on a scale Standard Deviation 1.15	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 12	-1 score on a scale Standard Deviation 2.83	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 13	-1 score on a scale Standard Deviation 2	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 14	-1.3 score on a scale Standard Deviation 1.53	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 18	0 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 19	-0.5 score on a scale Standard Deviation 2.12	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 23	0 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 26	-1 score on a scale Standard Deviation 2	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 30	-0.7 score on a scale Standard Deviation 1.53	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 33	-2 score on a scale Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 34	-0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 35	-1 score on a scale Standard Deviation 1	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 36	-1 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 37	-0.8 score on a scale Standard Deviation 0.5	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 38	-1 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 39	-1 score on a scale Standard Deviation 1.41	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 40	-1.3 score on a scale Standard Deviation 2.08	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 41	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 44	0 score on a scale Standard Deviation 1.41	—	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 28 (assessed daily)

Population: No data collection for field with 0 participants.

The NRS of pain intensity is a unidimensional, segmented numeric version of the visual analog scale. A subject selects a whole number (0 to 10) that best indicates the intensity of his/her pain. The format consists of a horizontal line which is anchored by terms defining pain levels where 0 represents no pain and 10 represents worst pain imaginable.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 3	-1.4 units on a scale Standard Deviation 2.51	—	—	0 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 4	-0.3 units on a scale Standard Deviation 3.21	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 7	-0.7 units on a scale Standard Deviation 2.89	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 10	-2 units on a scale Standard Deviation 2.83	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 11	-1 units on a scale Standard Deviation 2.65	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 12	-2 units on a scale Standard Deviation 2.83	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 13	-1.3 units on a scale Standard Deviation 3.21	—	—	-13 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 21	-2 units on a scale Standard Deviation 2.83	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 22	-2 units on a scale Standard Deviation 2.28	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 23	0 units on a scale Standard Deviation 1.41	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 25	-2.5 units on a scale Standard Deviation 2.12	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 27	-1.5 units on a scale Standard Deviation 0.71	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 28	-1.5 units on a scale Standard Deviation 1.91	—	—	1 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 1	0 units on a scale Standard Deviation 0	—	—	0 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 2	-1.3 units on a scale Standard Deviation 1.89	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 5	-1 units on a scale Standard Deviation 2.65	—	—	-1 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 6	-0.3 units on a scale Standard Deviation 3.21	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 8	-1.8 units on a scale Standard Deviation 3.2	—	—	-0.5 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 9	-0.5 units on a scale Standard Deviation 3	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 14	-1 units on a scale Standard Deviation 2.65	—	—	-1 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 15	-2 units on a scale Standard Deviation 2.31	—	—	-1 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 16	-0.5 units on a scale Standard Deviation 2.38	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 17	-2 units on a scale Standard Deviation 2.83	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 18	-2 units on a scale Standard Deviation 2.83	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 19	-2 units on a scale Standard Deviation 2.83	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 20	-2 units on a scale Standard Deviation 2.83	—	—	—
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 24	-1.7 units on a scale Standard Deviation 3.06	—	—	-2 units on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 26	-1.7 units on a scale Standard Deviation 3.06	—	—	—

SECONDARY outcome

Timeframe: Baseline through Day 51 (assessed daily)

Population: No data collection for field with 0 participants.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 41	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 42	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 43	0 score on a scale Standard Deviation 0	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 3	0.2 score on a scale Standard Deviation 1.3	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 4	0 score on a scale Standard Deviation 1	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 5	0 score on a scale Standard Deviation 1	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 10	0.5 score on a scale Standard Deviation 0.71	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 11	1 score on a scale Standard Deviation 1	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 12	-0.5 score on a scale Standard Deviation 2.12	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 13	0.3 score on a scale Standard Deviation 0.58	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 14	0 score on a scale Standard Deviation 0	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 15	0 score on a scale Standard Deviation 0	—	—	-0.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 16	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 18	1.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 19	1.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 20	0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 21	-1 score on a scale Standard Deviation 1.41	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 22	0 score on a scale Standard Deviation 0.89	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 27	1.5 score on a scale Standard Deviation 0.71	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 28	0.5 score on a scale Standard Deviation 0.58	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 30	0.3 score on a scale Standard Deviation 0.58	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 31	0.3 score on a scale Standard Deviation 0.58	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 32	0.5 score on a scale Standard Deviation 0.71	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 33	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 36	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 40	0.7 score on a scale Standard Deviation 1.15	—	—	1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 44	1.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 45	1 score on a scale Standard Deviation 1.41	—	—	-2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 1	0 score on a scale Standard Deviation 0.63	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 2	-0.8 score on a scale Standard Deviation 0.96	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 6	0.7 score on a scale Standard Deviation 0.58	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 7	0.3 score on a scale Standard Deviation 0.58	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 8	0.3 score on a scale Standard Deviation 0.96	—	—	-0.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 9	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 17	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 23	0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 24	0.3 score on a scale Standard Deviation 0.58	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 25	0.5 score on a scale Standard Deviation 0.71	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 26	0 score on a scale Standard Deviation 1	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 29	1.3 score on a scale Standard Deviation 0.58	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 34	1 score on a scale Standard Deviation 1.41	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 35	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 37	0.5 score on a scale Standard Deviation 1	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 38	0 score on a scale Standard Deviation 0	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 39	0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 46	1 score on a scale Standard Deviation 1.41	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 47	2 score on a scale Standard Deviation 1.41	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 48	1 score on a scale Standard Deviation 0	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 49	0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 50	0.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Day 51	1 score on a scale Standard Deviation 0	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.

SECONDARY outcome

Timeframe: Day 1 through Day 28 (assessed daily)

Population: No data collection for field with 0 participants.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 1	0 score on a scale Standard Deviation 0	—	—	0 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 5	-1 score on a scale Standard Deviation 1.73	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 6	0.3 score on a scale Standard Deviation 1.15	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 8	-1.8 score on a scale Standard Deviation 2.06	—	—	0.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 9	-0.8 score on a scale Standard Deviation 2.36	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 21	-3 score on a scale Standard Deviation 1.41	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 22	-2.7 score on a scale Standard Deviation 1.97	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 23	-1 score on a scale Standard Deviation 2.83	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 26	-2 score on a scale Standard Deviation 2.65	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 2	-2.3 score on a scale Standard Deviation 1.53	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 3	-1.6 score on a scale Standard Deviation 1.82	—	—	-2.5 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 4	-0.7 score on a scale Standard Deviation 2.89	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 7	-1 score on a scale Standard Deviation 2.65	—	—	-2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 10	-3 score on a scale Standard Deviation 1.41	—	—	-4 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 11	-1.7 score on a scale Standard Deviation 2.52	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 12	-3 score on a scale Standard Deviation 1.41	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 13	-2 score on a scale Standard Deviation 3	—	—	-2 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 14	-1 score on a scale Standard Deviation 1.73	—	—	-1 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 15	-2.8 score on a scale Standard Deviation 0.96	—	—	-1.3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 16	-0.8 score on a scale Standard Deviation 2.06	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 17	-3 score on a scale Standard Deviation 1.41	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 18	-2.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 19	-2.5 score on a scale Standard Deviation 0.71	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 20	-3 score on a scale Standard Deviation 1.41	—	—	—
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 24	-2 score on a scale Standard Deviation 2.65	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 25	-2.5 score on a scale Standard Deviation 0.71	—	—	-3 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 27	-0.5 score on a scale Standard Deviation 3.54	—	—	-4 score on a scale Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 28	-0.5 score on a scale Standard Deviation 1.73	—	—	—

SECONDARY outcome

Timeframe: Baseline through Day 28

Population: No data collection for field with 0 participants.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 3	-65 MME (morphine milligram equivalent) Standard Deviation 49.5	—	—	-45 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 24	-20 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 1	-100 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	-45 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 2	-30 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	-45 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 4	-63.3 MME (morphine milligram equivalent) Standard Deviation 35.12	—	—	-45 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 5	-66.7 MME (morphine milligram equivalent) Standard Deviation 40.41	—	—	-45 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 6	-80 MME (morphine milligram equivalent) Standard Deviation 62.45	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 7	-75 MME (morphine milligram equivalent) Standard Deviation 25.98	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 8	-60.8 MME (morphine milligram equivalent) Standard Deviation 34.13	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 9	-93.3 MME (morphine milligram equivalent) Standard Deviation 50.08	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 10	-45 MME (morphine milligram equivalent) Standard Deviation 0	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 11	-78.3 MME (morphine milligram equivalent) Standard Deviation 29.3	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 12	-67.5 MME (morphine milligram equivalent) Standard Deviation 31.82	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 13	-78.3 MME (morphine milligram equivalent) Standard Deviation 29.3	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 14	-145 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 16	-155 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 20	—	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 22	-15 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 23	-20 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 25	—	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 27	—	—	—	-67.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose Expressed as Morphine Equivalent Dose (MED) Day 28	-20 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—

SECONDARY outcome

Timeframe: Baseline through Day 28

Population: No data collection for field with 0 participants.

Outcome measures

Outcome measures
Measure	Placebo Severity of Opiate Withdrawal Averages: n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine Side Effects Index Averages: Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo Side Effects Index Averages: Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 4	-50 MME (morphine milligram equivalent) Standard Deviation 0	—	—	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 23	-10 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 24	-10 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 1	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 2	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 3	-50 MME (morphine milligram equivalent) Standard Deviation 0	—	—	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 5	-51.7 MME (morphine milligram equivalent) Standard Deviation 2.89	—	—	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 6	-58.3 MME (morphine milligram equivalent) Standard Deviation 14.43	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 7	-65 MME (morphine milligram equivalent) Standard Deviation 17.32	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 8	-52.1 MME (morphine milligram equivalent) Standard Deviation 21.95	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 9	-74.2 MME (morphine milligram equivalent) Standard Deviation 1.44	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 10	-56.3 MME (morphine milligram equivalent) Standard Deviation 26.52	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 11	-66.7 MME (morphine milligram equivalent) Standard Deviation 14.43	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 12	-75 MME (morphine milligram equivalent) Standard Deviation 0	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 13	-66.7 MME (morphine milligram equivalent) Standard Deviation 14.43	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 14	-72.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 16	-77.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 20	—	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 22	-7.5 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 25	—	—	—	-75 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 27	—	—	—	-50 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant in Lofexidine group.
Change in Daily Opioid Dose as a Percentage of the Baseline MED Day 28	-10 MME (morphine milligram equivalent) Standard Deviation NA No standard deviation because only 1 participant with recorded data.	—	—	—

Adverse Events

Lofexidine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lofexidine n=1 participants at risk Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo n=3 participants at risk Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Gastrointestinal disorders Diarrhoea	0.00% 0/1 • Day 1 of drug administration through 30 day follow up, up to 57 days.	33.3% 1/3 • Day 1 of drug administration through 30 day follow up, up to 57 days.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/1 • Day 1 of drug administration through 30 day follow up, up to 57 days.	33.3% 1/3 • Day 1 of drug administration through 30 day follow up, up to 57 days.
Skin and subcutaneous tissue disorders Rash	0.00% 0/1 • Day 1 of drug administration through 30 day follow up, up to 57 days.	33.3% 1/3 • Day 1 of drug administration through 30 day follow up, up to 57 days.
Respiratory, thoracic and mediastinal disorders Yawning	0.00% 0/1 • Day 1 of drug administration through 30 day follow up, up to 57 days.	33.3% 1/3 • Day 1 of drug administration through 30 day follow up, up to 57 days.
Nervous system disorders Lethargy	0.00% 0/1 • Day 1 of drug administration through 30 day follow up, up to 57 days.	33.3% 1/3 • Day 1 of drug administration through 30 day follow up, up to 57 days.

Additional Information

Medical Affairs

USWM, LLC

Phone: 1-888-900-8796

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lofexidine n=1 Participants Lofexidine: Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Placebo n=3 Participants Placebo: Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.	Total n=4 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	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	3 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