TABLE 2.
Summary of Adverse Events and Study Discontinuation (Modified Intent-to-Treat Population)
| Subject Experience, No. (%) | Placebo (n = 151) | Lofexidine 2.16 mg (n = 229) | Lofexidine 2.88 mg (n = 222) |
| At least 1 AE | 134 (88.7) | 216 (94.3) | 211 (95.0) |
| Opioid withdrawal-related AE* | 128 (84.8) | 181 (79.0) | 177 (79.7) |
| Nonopioid withdrawal-related AE* | 61 (40.4) | 176 (76.9) | 176 (79.3) |
| AE leading to study discontinuation | 44 (29.1) | 43 (18.8) | 55 (24.8) |
| Common AEs (>10%) | |||
| Insomnia | 73 (48.3) | 117 (51.1) | 123 (55.4) |
| Orthostatic hypotension† | 7 (4.6) | 67 (29.3) | 94 (42.3) |
| Bradycardia† | 8 (5.3) | 54 (23.6) | 70 (31.5) |
| Hypotension† | 2 (1.3) | 69 (30.1) | 67 (30.2) |
| Dizziness | 4 (2.6) | 44 (19.2) | 51 (23.0) |
| Diarrhea | 35 (23.2) | 51 (22.3) | 48 (21.6) |
| Pain | 36 (23.8) | 51 (22.3) | 42 (18.9) |
| Headache | 23 (15.2) | 30 (13.1) | 31 (14.0) |
| Somnolence | 8 (5.3) | 25 (10.9) | 29 (13.1) |
| Nausea | 32 (21.2) | 50 (21.8) | 27 (12.2) |
| Sedation | 8 (5.3) | 29 (12.7) | 27 (12.2) |
| Dry mouth | 0 | 22 (9.6) | 24 (10.8) |
| Myalgia | 25 (16.6) | 30 (13.1) | 22 (9.9) |
| Vomiting | 24 (15.9) | 23 (10.0) | 19 (8.6) |
| Study discontinuation | 109 (72.2) | 135 (59.0) | 134 (60.4) |
| Lack of efficacy | 53 (35.1) | 44 (19.1) | 30 (13.5) |
| Study drug-related AE | 2 (1.3) | 15 (6.5) | 30 (13.5) |
| Withdrawal of consent | 18 (11.9) | 30 (13.1) | 36 (16.2) |
| Personal/family reasons | 15 (9.9) | 14 (6.1) | 17 (7.7) |
| Other‡ | 21 (13.9) | 32 (14.0) | 21 (9.5) |
*Study investigators were required to judge whether AEs were related to opioid withdrawal at the time AEs were assessed.
†Orthostatic hypotension, hypotension, and bradycardia were required to be reported as AEs if predefined criteria were met: systolic blood pressure <90 mm Hg, diastolic blood pressure <50 mm Hg, pulse rate <50 beats/min, or >20% decrease from screening; decrease in standing systolic or diastolic blood pressure >25% from recumbent values.
‡Includes nonrelated AEs, lack of adherence, evidence of contraband drug use, therapy with exclusionary drug, intensive cravings, did not want to continue inpatient, left against medical advice, completed detoxification, and protocol nonadherence.
AE, adverse event.