Table 4.
Treatment-Emergent Adverse Events and Serious Adverse Events by Treatment Arm
| PLB (N=102) | BUP4 (N=100) | BUP16 (N=100) | |
|---|---|---|---|
| ADVERSE EVENTS (AEs) | |||
| % (n) Participants with treatment-emergent AEs | 59.8% (61) | 66.0% (66) | 64.0% (64) |
| Number of treatment-emergent AEs | 145 | 192 | 209 |
| Severity of treatment-emergent AEs, % (n) | |||
| Grade 1 – Mild | 55.2% (80) | 53.6% (103) | 61.2% (128) |
| Grade 2 – Moderate | 32.4% (47) | 41.7% (80) | 34.9% (73) |
| Grade 3 – Severe | 12.4% (18) | 4.7% (9) | 3.8% (8) |
| Relationship of treatment-emergent AEs, % (n) | |||
| Not related | 39.3% (57) | 32.8% (63) | 29.7% (62) |
| Causal relationship to naltrexone only | 21.4% (31) | 23.4% (45) | 20.1% (42) |
| Causal relationship to buprenorphine/placebo only | 21.4% (31) | 21.9% (42) | 34.4% (72) |
| Causal relationship to buprenorphine/placebo and naltrexone | 17.9% (26) | 21.9% (42) | 15.8% (33) |
| Types of AEs deemed possibly/definitely-related to buprenorphine (n) | 57 | 84 | 105 |
| Abdominal cramps, upset stomach | 2 | 1 | 1 |
| Acid reflux | 1 | 0 | 0 |
| Anxiety, subjective anxiety | 0 | 0 | 4 |
| Brief psychotic episode | 0 | 1 | 0 |
| Change in smell, taste, bitter metallic taste | 0 | 1 | 2 |
| Sweats, cold sweats, night sweats | 1 | 2 | 4 |
| Constipation, hard stools | 9 | 9 | 12 |
| Decreased/loss of appetite | 1 | 3 | 2 |
| Decreased libido, sex drive | 2 | 1 | 0 |
| Depressed mood | 1 | 0 | 0 |
| Diarrhea | 2 | 0 | 4 |
| Disoriented, mental cloudiness | 0 | 0 | 2 |
| Dizziness, lightheaded | 5 | 9 | 10 |
| Drowsiness, sedation, sleepiness | 1 | 3 | 6 |
| Opiate/drug withdrawal symptoms | 2 | 2 | 1 |
| Dry mouth | 3 | 0 | 3 |
| Elevated liver function | 0 | 1 | 0 |
| Fatigue | 2 | 4 | 3 |
| Feeling high, euphoria | 0 | 1 | 1 |
| Gagging on medication | 0 | 0 | 1 |
| General body soreness, musculoskeletal pain/cramps | 2 | 1 | 0 |
| Headache | 1 | 1 | 3 |
| Hematemesis | 0 | 0 | 1 |
| Hot flashes | 0 | 1 | 1 |
| Increased opiate craving | 1 | 0 | 0 |
| Insomnia, interrupted sleep | 2 | 3 | 1 |
| Irritable mood | 0 | 2 | 0 |
| Itching | 0 | 0 | 3 |
| Leg restlessness | 0 | 1 | 0 |
| Loss of consciousness | 0 | 0 | 1 |
| Nausea | 13 | 24 | 23 |
| Nervousness, restlessness | 0 | 1 | 2 |
| Runny nose | 0 | 1 | 0 |
| Sensitive teeth | 1 | 0 | 0 |
| Sluggishness | 0 | 0 | 2 |
| Tearing | 0 | 1 | 0 |
| Tinnitus | 0 | 0 | 1 |
| Urinary retention | 0 | 0 | 1 |
| Vomiting | 5 | 10 | 10 |
| SERIOUS ADVERSE EVENTS (SAEs) | |||
| % (n) Participants with treatment-emergent SAEs | 11.8% (12) | 13.0% (13) | 8.0% (8) |
| Number of treatment-emergent SAEs | 14 | 14 | 9 |
| Relationship of treatment-emergent SAEs, % (n) | |||
| Not related as assessed by Medical Monitor | 100% (14) | 100% (14) | 100% (9) |
| Type of SAEs (n) | |||
| Death | 1 | 0 | 0 |
| Inpatient admission to hospital | 13 | 14 | 9 |