Trial Outcomes & Findings for Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM) to Treat OPIOID Withdrawal (NCT NCT04218240)
NCT ID: NCT04218240
Last Updated: 2024-09-19
Results Overview
mild = 1-10 moderate=11-20 severe=21-30 higher number equals worse score
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
90 participants
Primary outcome timeframe
7 days
Results posted on
2024-09-19
Participant Flow
Participants were recruited based on media advertising from 3 treatment programs between December 2020 and March 2023. The first participant was enrolled on December 17, 2020 and the last participant was enrolled on 3/1/2023.
90 consented and enrolled participants who met inclusion criteria and were randomized 1:1 ratio of either active pregabalin + lofexidine, or placebo pregabalin + lofexidine.
Participant milestones
| Measure |
PGB/LFX;
oral tablet-lofexidine-active; oral capsule pregabalin-active Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin at 25 mg; 8am,12p, 4p, and 8p.
|
Lofexidine and PLACEBO
oral tablet-lofexidine-active; oral capsule pregabalin-placebo Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin-placebo starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin-placebo starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin-placebo at 25 mg; 8am,12p, 4p, and 8p.
|
|---|---|---|
|
Overall Study
STARTED
|
58
|
32
|
|
Overall Study
COMPLETED
|
24
|
11
|
|
Overall Study
NOT COMPLETED
|
34
|
21
|
Reasons for withdrawal
| Measure |
PGB/LFX;
oral tablet-lofexidine-active; oral capsule pregabalin-active Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin at 25 mg; 8am,12p, 4p, and 8p.
|
Lofexidine and PLACEBO
oral tablet-lofexidine-active; oral capsule pregabalin-placebo Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin-placebo starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin-placebo starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin-placebo at 25 mg; 8am,12p, 4p, and 8p.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
6
|
0
|
|
Overall Study
Lack of Efficacy
|
24
|
19
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Not Dosed Never met WD criteria
|
4
|
1
|
Baseline Characteristics
Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM) to Treat OPIOID Withdrawal
Baseline characteristics by cohort
| Measure |
PGB/LFX;
n=58 Participants
0.54 mg lofexidine and 200 mg Pregabalin on days 1 -7 with taper for pregabalin and lofexidine starting on day 5
Pregabalin 200 MG capsules: oral pregabalin 200 mg capsules given with a taper on day 5
Lofexidine 0.18Mg Tab: lofexidine 0.18 tab given with a taper starting on day 5
|
Lofexidine and PLACEBO
n=32 Participants
0.54 mg lofexidine and Placebo (PLB) on days 1-7 with taper for lofexidine starting on day 5
Placebo oral tablet: oral Placebo
Lofexidine 0.18Mg Tab: lofexidine 0.18 tab given with a taper starting on day 5
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.4138 years
STANDARD_DEVIATION 10.40417 • n=99 Participants
|
37.6563 years
STANDARD_DEVIATION 10.2189 • n=107 Participants
|
38.7889 years
STANDARD_DEVIATION 10.3157 • n=206 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
69 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
54 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
86 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
32 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
10 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
58 participants
n=99 Participants
|
32 participants
n=107 Participants
|
90 participants
n=206 Participants
|
|
Fentanyl Use
|
53 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
83 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 7 daysPopulation: males, females 18+ years of age, opioid use disorder
mild = 1-10 moderate=11-20 severe=21-30 higher number equals worse score
Outcome measures
| Measure |
PGB/LFX;
n=58 Participants
oral tablet-lofexidine-active; oral capsule pregabalin-active Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin at 25 mg; 8am,12p, 4p, and 8p.
|
Lofexidine and PLACEBO
n=32 Participants
oral tablet-lofexidine-active; oral capsule pregabalin-placebo Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin-placebo starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin-placebo starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin-placebo at 25 mg; 8am,12p, 4p, and 8p.
|
|---|---|---|
|
Subjective Opioid Withdrawal Scale-Gossop (SOWS) Scale Score
|
7.0 score on a scale
Standard Deviation 4.6
|
9.1 score on a scale
Standard Deviation 5.1
|
SECONDARY outcome
Timeframe: 7 daysPopulation: male, females 18+ years of age, opioid Use diagnosis
proportion of participants who completed the 7-day detoxification
Outcome measures
| Measure |
PGB/LFX;
n=58 Participants
oral tablet-lofexidine-active; oral capsule pregabalin-active Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin at 25 mg; 8am,12p, 4p, and 8p.
|
Lofexidine and PLACEBO
n=32 Participants
oral tablet-lofexidine-active; oral capsule pregabalin-placebo Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin-placebo starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin-placebo starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin-placebo at 25 mg; 8am,12p, 4p, and 8p.
|
|---|---|---|
|
Completion of Withdrawal Management
completed detox
|
23 Participants
|
9 Participants
|
|
Completion of Withdrawal Management
did not complete detox
|
35 Participants
|
23 Participants
|
Adverse Events
PGB/LFX;
Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths
Lofexidine and PLACEBO
Serious events: 1 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PGB/LFX;
n=58 participants at risk
oral tablet-lofexidine-active; oral capsule pregabalin-active Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin at 25 mg; 8am,12p, 4p, and 8p.
|
Lofexidine and PLACEBO
n=32 participants at risk
oral tablet-lofexidine-active; oral capsule pregabalin-placebo Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin-placebo starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin-placebo starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin-placebo at 25 mg; 8am,12p, 4p, and 8p.
|
|---|---|---|
|
Gastrointestinal disorders
nausea with vomiting
|
0.00%
0/58 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
3.1%
1/32 • Number of events 1 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
Other adverse events
| Measure |
PGB/LFX;
n=58 participants at risk
oral tablet-lofexidine-active; oral capsule pregabalin-active Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin at 25 mg; 8am,12p, 4p, and 8p.
|
Lofexidine and PLACEBO
n=32 participants at risk
oral tablet-lofexidine-active; oral capsule pregabalin-placebo Day 1: 0.54 mg lofexidine 3 times/day starting at 12p; plus 100 mg Pregabalin-placebo starting at 12p, and 4p, 200 mg at 8p. Day 2 through 5: 0.54 mg of lofexidine 4 times/day starting at 8a; plus 200 mg of pregabalin-placebo starting at 8am, 100 mg at 12p and 4p; and 200 mg at 8p.
Taper starts on Day 5 for lofexidine at 0.54 at 8a, 0.36 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 100 mg, 75 mg at 12p, 4p, and 150 at 8p.
Taper on Day 6 for lofexidine at 0.36 at 8a, and 0.18 at 12p, 4p and 8p plus pregabalin-placebo starting at 8am at 50 mg, 25 mg at 12p, 4p, and 100 at 8p.
Taper on Day 7 for lofexidine at 0.18 mg at 8a; 12p; 4p and 8p plus pregabalin-placebo at 25 mg; 8am,12p, 4p, and 8p.
|
|---|---|---|
|
Vascular disorders
bradycardia
|
17.2%
10/58 • Number of events 12 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
21.9%
7/32 • Number of events 9 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
|
Nervous system disorders
dizziness
|
13.8%
8/58 • Number of events 8 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
25.0%
8/32 • Number of events 8 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
|
Cardiac disorders
orthostatic hypotension
|
53.4%
31/58 • Number of events 64 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
62.5%
20/32 • Number of events 42 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
|
Nervous system disorders
sedation
|
20.7%
12/58 • Number of events 13 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
18.8%
6/32 • Number of events 6 • 15 days per subject
Withdrawal, unless clinically excessive is not considered an adverse event. Otherwise, definition is universal.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place