Table 3.
Adverse Events That Occurred during the Trial Period.*
| Event | Stage 1 | Stage 2 | ||||
|---|---|---|---|---|---|---|
| Naltrexone–Bupropion (N = 109) | Placebo (N = 294) | P Value | Naltrexone–Bupropion (N = 114) | Placebo (N = 111) | P Value | |
| Participants with at least one serious adverse event — no. (%)† | 1 (0.9) | 4 (1.4) | 1.00 | 3 (2.6) | 4 (3.6) | 0.72 |
| Total no. of serious adverse events‡ | 1 | 4 | 4 | 4 | ||
| Any adverse event — no. (%) | 99 (90.8) | 245 (83.3) | 0.08 | 88 (77.2) | 77 (69.4) | 0.23 |
| Adverse events — no. (%)§ | ||||||
| Gastrointestinal events | ||||||
| Nausea | 41 (37.6) | 45 (15.3) | <0.001 | 32 (28.1) | 8 (7.2) | <0.001 |
| Diarrhea | 7 (6.4) | 18 (6.1) | 1.00 | 6 (5.3) | 5 (4.5) | 1.00 |
| Vomiting | 13 (11.9) | 6 (2.0) | <0.001 | 12 (10.5) | 3 (2.7) | 0.03 |
| Constipation | 10 (9.2) | 7 (2.4) | 0.005 | 2 (1.8) | 3 (2.7) | 0.68 |
| Dry mouth | 9 (8.3) | 5 (1.7) | 0.003 | 1 (0.9) | 2 (1.8) | 0.62 |
| Upper abdominal pain | 5 (4.6) | 1 (0.3) | 0.006 | 6 (5.3) | 3 (2.7) | 0.50 |
| Abdominal discomfort | 4 (3.7) | 5 (1.7) | 0.26 | 1 (0.9) | 2 (1.8) | 0.62 |
| Nervous system symptoms and disorders | ||||||
| Headache | 13 (11.9) | 68 (23.1) | 0.01 | 11 (9.6) | 6 (5.4) | 0.31 |
| Dizziness | 11 (10.1) | 8 (2.7) | 0.006 | 7 (6.1) | 1 (0.9) | 0.07 |
| Somnolence | 3 (2.8) | 10 (3.4) | 1.00 | 0 | 1 (0.9) | 0.49 |
| Tremor | 5 (4.6) | 1 (0.3) | 0.006 | 3 (2.6) | 0 | 0.25 |
| Psychiatric symptoms and disorders | ||||||
| Irritability | 6 (5.5) | 19 (6.5) | 0.82 | 5 (4.4) | 4 (3.6) | 1.00 |
| Anxiety | 10 (9.2) | 14 (4.8) | 0.10 | 1 (0.9) | 1 (0.9) | 1.00 |
| Insomnia | 6 (5.5) | 12 (4.1) | 0.59 | 3 (2.6) | 1 (0.9) | 0.62 |
| Libido decreased | 4 (3.7) | 5 (1.7) | 0.26 | 1 (0.9) | 0 | 1.00 |
| Lability affected | 4 (3.7) | 4 (1.4) | 0.22 | 2 (1.8) | 1 (0.9) | 1.00 |
| Depression | 2 (1.8) | 6 (2.0) | 1.00 | 4 (3.5) | 4 (3.6) | 1.00 |
| General disorders and injection-site reactions | ||||||
| Fatigue | 8 (7.3) | 33 (11.2) | 0.35 | 7 (6.1) | 8 (7.2) | 0.80 |
| Feeling jittery | 4 (3.7) | 2 (0.7) | 0.05 | 1 (0.9) | 0 | 1.00 |
| Malaise | 4 (3.7) | 1 (0.3) | 0.02 | 1 (0.9) | 0 | 1.00 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 8 (7.3) | 6 (2.0) | 0.03 | 3 (2.6) | 3 (2.7) | 1.00 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 4 (3.7) | 6 (2.0) | 0.47 | 2 (1.8) | 0 | 0.50 |
| Injury, poisoning, and procedural complications | ||||||
| Contusion | 3 (2.8) | 5 (1.7) | 0.45 | 0 | 5 (4.5) | 0.03 |
| Skin and subcutaneous tissue disorders | ||||||
| Hyperhidrosis | 8 (7.3) | 3 (1.0) | 0.002 | 2 (1.8) | 0 | 0.50 |
Events shown for stage 1 include events that occurred before the start of stage 2 in the safety population (all participants who underwent randomization). Events shown for stage 2 include those that occurred on or after the date of rerandomization in participants in the intention-to-treat population (participants who underwent randomization again in stage 2). Adverse events were classified according to the preferred term and system organ class of the Medical Dictionary for Regulatory Activities, version 22.1.
Of the 17 serious adverse events that occurred in the safety population (all participants who gave informed consent), 13 occurred in the intention-to-treat population and are reported in this table. Of the 13 serious adverse events, all except an event of seizure were recorded as serious because they resulted in either inpatient hospitalization or prolongation of an existing hospitalization. The additional 4 serious adverse events occurred after consent was given but before randomization; the events were hypertensive crisis (in 1 participant), genito-urinary chlamydia infection (in 1 participant), neurosyphilis (in 1 participant), and appendicitis (in 1 participant). Four additional adverse events occurred in stage 2 in participants who did not undergo rerandomization (3 events in the naltrexone–bupropion group and 1 in the placebo group).
The serious adverse events in stage 1 were substance-induced psychosis, paranoia, pancreatitis, and seizure (in 1 participant each) in the placebo group, and gastroenteritis in 1 participant in the naltrexone–bupropion group. The serious adverse events in stage 2 were gastroenteritis shigella, pneumonia, urosepsis, and being the victim of a crime (in 1 participant each) in the placebo group, and homicidal ideation, cellulitis, neck pain, and hyperglycemia (in 1 participant each) in the naltrexone–bupropion group.
The adverse events reported here are events of interest that occurred in 3% or more of participants in either stage in the naltrexone–bupropion group and events that had a P value of ≤0.05 for any pairwise comparison. Table S2 lists all adverse events that occurred during the trial in the safety population.