Trial Outcomes & Findings for Efficacy, Safety and Dose-Response Study Followed by Open-Label Study of Lofexidine Treatment of Opioid Withdrawal (NCT NCT01863186)

Last Updated: 2022-03-22

Results Overview

The SOWS-Gossop was completed by the mITT population subject at baseline, once daily at 3.5 hours after the first dose of the study medication on Days 1 to 7. It consists of 10 items that are scored on a 4-point scale; 0=none, 1=mild, 2=moderate, and 3=severe. The overall score is the simple sum of the 10-item scores (minimum overall score of 0, maximum score of 30). Higher individual scores on the scale indicate greater symptom severity. However, as the outcome measure is a difference from placebo, a lower number indicates a better outcome. mITT population: all randomized subjects who received at least 1 dose of study medication

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

603 participants

Primary outcome timeframe

Days 1 through 7

Results posted on

2022-03-22

Participant Flow

Participant milestones

Participant milestones
Measure	DB: Lofexidine HCl 2.4mg Dose Participants were randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.	DB: Lofexidine HCl 3.2mg Dose Participants were randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.	DB: Placebo Participants were randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days. Placebo: Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.	OL: All Lofexidine HCl Participants were given the option to receive lofexidine HCl tablets for up to 7 additional days, following the double blind period. Dosing regimens are at the discretion of the Investigator, but total daily dose will not exceed 3.2 mg.
Double-blind Phase STARTED	229	222	151	0
Double-blind Phase COMPLETED	95	88	42	0
Double-blind Phase NOT COMPLETED	134	134	109	0
Open-label Phase STARTED	0	0	0	83
Open-label Phase COMPLETED	0	0	0	70
Open-label Phase NOT COMPLETED	0	0	0	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy, Safety and Dose-Response Study Followed by Open-Label Study of Lofexidine Treatment of Opioid Withdrawal

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DB: Lofexidine HCl 2.4mg Dose n=229 Participants Participants were randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.	DB: Lofexidine HCl 3.2mg Dose n=222 Participants Participants were randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.	DB: Placebo n=151 Participants Participants were randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days. Placebo: Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.	Total n=602 Participants Total of all reporting groups
Age, Continuous	35 years STANDARD_DEVIATION 10.8 • n=5 Participants	35 years STANDARD_DEVIATION 10.5 • n=7 Participants	36 years STANDARD_DEVIATION 11.9 • n=5 Participants	35 years STANDARD_DEVIATION 11.0 • n=4 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	64 Participants n=7 Participants	44 Participants n=5 Participants	175 Participants n=4 Participants
Sex: Female, Male Male	162 Participants n=5 Participants	158 Participants n=7 Participants	107 Participants n=5 Participants	427 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=5 Participants	28 Participants n=7 Participants	22 Participants n=5 Participants	83 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	196 Participants n=5 Participants	194 Participants n=7 Participants	129 Participants n=5 Participants	519 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Black or African American	54 Participants n=5 Participants	48 Participants n=7 Participants	26 Participants n=5 Participants	128 Participants n=4 Participants
Race (NIH/OMB) White	169 Participants n=5 Participants	158 Participants n=7 Participants	117 Participants n=5 Participants	444 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	16 Participants n=4 Participants
Body weight	76.0 kg STANDARD_DEVIATION 16.88 • n=5 Participants	76.1 kg STANDARD_DEVIATION 16.59 • n=7 Participants	76.0 kg STANDARD_DEVIATION 14.94 • n=5 Participants	76.1 kg STANDARD_DEVIATION 16.29 • n=4 Participants
BMI (kg/m^2)	25.1 kg/m^2 STANDARD_DEVIATION 4.71 • n=5 Participants	25.1 kg/m^2 STANDARD_DEVIATION 5.32 • n=7 Participants	25.1 kg/m^2 STANDARD_DEVIATION 4.63 • n=5 Participants	25.1 kg/m^2 STANDARD_DEVIATION 4.92 • n=4 Participants

PRIMARY outcome

Timeframe: Days 1 through 7

Population: mITT population Participants Analyzed does not match the Participant Flow because of missing data.

Outcome measures

Outcome measures
Measure	DB: Lofexidine HCl 2.4mg Dose n=229 Participants Participants were randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.	DB: Lofexidine HCl 3.2mg Dose n=222 Participants Participants were randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.	DB: Placebo n=151 Participants Participants were randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days. Placebo: Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 7	2.7 score on a scale Standard Deviation 3.45	2.3 score on a scale Standard Deviation 3.23	2.7 score on a scale Standard Deviation 4.60
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 1	7.8 score on a scale Standard Deviation 6.00	7.6 score on a scale Standard Deviation 6.75	9.4 score on a scale Standard Deviation 6.81
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 2	10.2 score on a scale Standard Deviation 6.83	9.9 score on a scale Standard Deviation 7.38	13.9 score on a scale Standard Deviation 8.29
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 3	7.6 score on a scale Standard Deviation 5.53	7.4 score on a scale Standard Deviation 6.34	10.9 score on a scale Standard Deviation 6.76
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 4	5.7 score on a scale Standard Deviation 5.32	5.5 score on a scale Standard Deviation 5.36	9.2 score on a scale Standard Deviation 6.81
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 5	4.7 score on a scale Standard Deviation 4.60	4.5 score on a scale Standard Deviation 4.96	6.4 score on a scale Standard Deviation 5.91
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores Day 6	3.6 score on a scale Standard Deviation 3.97	3.2 score on a scale Standard Deviation 4.10	4.4 score on a scale Standard Deviation 5.80

SECONDARY outcome

Timeframe: Day 7

Population: The percentage of subjects in each treatment arm who complete the double-blind phase of the study (defined as those who receive at least one dose of study medication on Day 7 and complete the 3.5 hour post-dose SOWS-Gossop assessment on Day 7).

The percentage of subjects in each treatment arm who receive at least one dose of study medication on Day 7 and complete the 3.5 hour post-dose SOWS-Gossop assessment on Day 7.

Outcome measures

Outcome measures
Measure	DB: Lofexidine HCl 2.4mg Dose n=229 Participants Participants were randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.	DB: Lofexidine HCl 3.2mg Dose n=222 Participants Participants were randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.	DB: Placebo n=151 Participants Participants were randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days. Placebo: Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.
Completion Status Yes/Complete	95 Participants	88 Participants	42 Participants
Completion Status No/Did Not Complete	134 Participants	134 Participants	109 Participants

Adverse Events

DB: Lofexidine HCl 2.4mg Dose

Serious events: 0 serious events

Other events: 216 other events

Deaths: 0 deaths

DB: Lofexidine HCl 3.2mg Dose

Serious events: 5 serious events

Other events: 211 other events

Deaths: 1 deaths

DB: Placebo

Serious events: 2 serious events

Other events: 134 other events

Deaths: 0 deaths

OL: All Lofexidine HCl

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DB: Lofexidine HCl 2.4mg Dose n=229 participants at risk Participants were randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.	DB: Lofexidine HCl 3.2mg Dose n=222 participants at risk Participants were randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.	DB: Placebo n=151 participants at risk Participants were randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days. Placebo: Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.	OL: All Lofexidine HCl n=83 participants at risk Participants were given the option to receive lofexidine HCl tablets for up to 7 additional days, following the double blind period. Dosing regimens are at the discretion of the Investigator, but total daily dose will not exceed 3.2 mg.
Infections and infestations Acute hepatitis C	0.00% 0/229 • Through study completion (14 Days)	0.00% 0/222 • Through study completion (14 Days)	0.66% 1/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Injury, poisoning and procedural complications Overdose	0.00% 0/229 • Through study completion (14 Days)	0.45% 1/222 • Through study completion (14 Days)	0.00% 0/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/229 • Through study completion (14 Days)	0.45% 1/222 • Through study completion (14 Days)	0.00% 0/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Investigations Electrocardiogram QT prolonged	0.00% 0/229 • Through study completion (14 Days)	0.00% 0/222 • Through study completion (14 Days)	0.66% 1/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Nervous system disorders Syncope	0.00% 0/229 • Through study completion (14 Days)	0.90% 2/222 • Through study completion (14 Days)	0.00% 0/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Psychiatric disorders Suicidal ideation	0.00% 0/229 • Through study completion (14 Days)	0.45% 1/222 • Through study completion (14 Days)	0.00% 0/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)

Other adverse events

Other adverse events
Measure	DB: Lofexidine HCl 2.4mg Dose n=229 participants at risk Participants were randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.	DB: Lofexidine HCl 3.2mg Dose n=222 participants at risk Participants were randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.	DB: Placebo n=151 participants at risk Participants were randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days. Placebo: Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.	OL: All Lofexidine HCl n=83 participants at risk Participants were given the option to receive lofexidine HCl tablets for up to 7 additional days, following the double blind period. Dosing regimens are at the discretion of the Investigator, but total daily dose will not exceed 3.2 mg.
General disorders Drug withdrawal syndrome	6.1% 14/229 • Through study completion (14 Days)	6.3% 14/222 • Through study completion (14 Days)	4.6% 7/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
General disorders Fatigue	6.1% 14/229 • Through study completion (14 Days)	7.2% 16/222 • Through study completion (14 Days)	4.0% 6/151 • Through study completion (14 Days)	3.6% 3/83 • Through study completion (14 Days)
Musculoskeletal and connective tissue disorders Back pain	3.9% 9/229 • Through study completion (14 Days)	4.1% 9/222 • Through study completion (14 Days)	6.0% 9/151 • Through study completion (14 Days)	2.4% 2/83 • Through study completion (14 Days)
Musculoskeletal and connective tissue disorders Myalgia	13.1% 30/229 • Through study completion (14 Days)	9.9% 22/222 • Through study completion (14 Days)	16.6% 25/151 • Through study completion (14 Days)	1.2% 1/83 • Through study completion (14 Days)
Nervous system disorders Headache	13.1% 30/229 • Through study completion (14 Days)	14.0% 31/222 • Through study completion (14 Days)	15.2% 23/151 • Through study completion (14 Days)	4.8% 4/83 • Through study completion (14 Days)
Nervous system disorders Sedation	12.7% 29/229 • Through study completion (14 Days)	12.2% 27/222 • Through study completion (14 Days)	5.3% 8/151 • Through study completion (14 Days)	1.2% 1/83 • Through study completion (14 Days)
Nervous system disorders Dizziness	19.2% 44/229 • Through study completion (14 Days)	23.0% 51/222 • Through study completion (14 Days)	2.6% 4/151 • Through study completion (14 Days)	3.6% 3/83 • Through study completion (14 Days)
Nervous system disorders Somnolence	10.9% 25/229 • Through study completion (14 Days)	13.1% 29/222 • Through study completion (14 Days)	5.3% 8/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Psychiatric disorders Anxiety	4.4% 10/229 • Through study completion (14 Days)	4.5% 10/222 • Through study completion (14 Days)	6.6% 10/151 • Through study completion (14 Days)	6.0% 5/83 • Through study completion (14 Days)
Psychiatric disorders Insomnia	51.1% 117/229 • Through study completion (14 Days)	55.4% 123/222 • Through study completion (14 Days)	48.3% 73/151 • Through study completion (14 Days)	4.8% 4/83 • Through study completion (14 Days)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.5% 8/229 • Through study completion (14 Days)	2.7% 6/222 • Through study completion (14 Days)	6.0% 9/151 • Through study completion (14 Days)	1.2% 1/83 • Through study completion (14 Days)
Respiratory, thoracic and mediastinal disorders Cough	5.7% 13/229 • Through study completion (14 Days)	3.6% 8/222 • Through study completion (14 Days)	2.6% 4/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Vascular disorders Hypertension	1.3% 3/229 • Through study completion (14 Days)	3.2% 7/222 • Through study completion (14 Days)	9.9% 15/151 • Through study completion (14 Days)	1.2% 1/83 • Through study completion (14 Days)
Vascular disorders Hypotension	30.1% 69/229 • Through study completion (14 Days)	30.2% 67/222 • Through study completion (14 Days)	1.3% 2/151 • Through study completion (14 Days)	8.4% 7/83 • Through study completion (14 Days)
Vascular disorders Orthostatic hypotension	29.3% 67/229 • Through study completion (14 Days)	42.3% 94/222 • Through study completion (14 Days)	4.6% 7/151 • Through study completion (14 Days)	4.8% 4/83 • Through study completion (14 Days)
Cardiac disorders Tachycardia	2.6% 6/229 • Through study completion (14 Days)	0.90% 2/222 • Through study completion (14 Days)	8.6% 13/151 • Through study completion (14 Days)	6.0% 5/83 • Through study completion (14 Days)
Cardiac disorders Bradycardia	23.6% 54/229 • Through study completion (14 Days)	31.5% 70/222 • Through study completion (14 Days)	5.3% 8/151 • Through study completion (14 Days)	3.6% 3/83 • Through study completion (14 Days)
Gastrointestinal disorders Abdominal pain	3.9% 9/229 • Through study completion (14 Days)	2.3% 5/222 • Through study completion (14 Days)	6.0% 9/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Gastrointestinal disorders Abdominal pain upper	8.3% 19/229 • Through study completion (14 Days)	8.1% 18/222 • Through study completion (14 Days)	7.9% 12/151 • Through study completion (14 Days)	4.8% 4/83 • Through study completion (14 Days)
Gastrointestinal disorders Diarrhoea	22.3% 51/229 • Through study completion (14 Days)	21.6% 48/222 • Through study completion (14 Days)	23.2% 35/151 • Through study completion (14 Days)	6.0% 5/83 • Through study completion (14 Days)
Gastrointestinal disorders Dry mouth	9.6% 22/229 • Through study completion (14 Days)	10.8% 24/222 • Through study completion (14 Days)	1.3% 2/151 • Through study completion (14 Days)	4.8% 4/83 • Through study completion (14 Days)
Gastrointestinal disorders Constipation	6.1% 14/229 • Through study completion (14 Days)	7.7% 17/222 • Through study completion (14 Days)	2.6% 4/151 • Through study completion (14 Days)	2.4% 2/83 • Through study completion (14 Days)
Gastrointestinal disorders Nausea	21.8% 50/229 • Through study completion (14 Days)	12.2% 27/222 • Through study completion (14 Days)	21.2% 32/151 • Through study completion (14 Days)	0.00% 0/83 • Through study completion (14 Days)
Gastrointestinal disorders Vomiting	10.0% 23/229 • Through study completion (14 Days)	8.6% 19/222 • Through study completion (14 Days)	15.9% 24/151 • Through study completion (14 Days)	1.2% 1/83 • Through study completion (14 Days)
General disorders Pain	22.3% 51/229 • Through study completion (14 Days)	18.9% 42/222 • Through study completion (14 Days)	23.8% 36/151 • Through study completion (14 Days)	4.8% 4/83 • Through study completion (14 Days)

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place