Table 1.
Baseline Characteristics, Reasons for Early Withdrawal from the Study, and Adverse Events.*
| Variable | European Union Trial | U.S. Trial | ||
|---|---|---|---|---|
| Afamelanotide (N = 38) | Placebo (N = 36) | Afamelanotide (N = 48) | Placebo (N = 45) | |
| Age — yr | 38.3±13.0 | 38.6±11.6 | 40.4±12 | 39.1±16.2 |
| Body-mass index† | 24.0±3.0 | 26.5±5.2 | 26±4.8 | 26.7±5.4 |
| White race — no. (%)‡ | 38 (100) | 35 (97) | 47 (98) | 43 (96) |
| Fitzpatrick skin type — % | ||||
| I (never tans, always burns) | 16 | 33 | 27 | 22 |
| II (tans less than average [with difficulty], mostly burns) | 47 | 42 | 42 | 33 |
| III (tans at average level, sometimes has mild burn) | 34 | 25 | 25 | 36 |
| IV (rarely burns, tans more than average [with ease]) | 3 | 0 | 6 | 9 |
| Early discontinuation — no. of patients§ | 4 | 2 | 3 | 4 |
| Protocol violation | 1 | 0 | 0 | 0 |
| Suspected pregnancy | 1 | 0 | 0 | 0 |
| Withdrawal of consent | 2 | 1 | 2 | 0 |
| Lost to follow-up | 0 | 0 | 0 | 2 |
| Sponsor decision | 0 | 0 | 0 | 1 |
| Physician decision | 0 | 1 | 1 | 1 |
| Adverse events | ||||
| Adverse events that occurred during the study period — no. | 189 | 166 | 272 | 216 |
| Patients with any adverse event that occurred during the study period — no. (%) | 34 (89) | 32 (89) | 45 (94) | 39 (87) |
| Severity of adverse events that occurred during the study period — no. (%) | ||||
| Mild | 19 (50) | 17 (47) | 17 (35) | 14 (31) |
| Moderate | 12 (32) | 14 (39) | 25 (52) | 23 (51) |
| Severe | 3 (8) | 1 (3) | 3 (6) | 2 (4) |
| Most frequent adverse events that occurred during the study period — no. (%) | ||||
| Nausea | 7 (18) | 6 (17) | 9 (19) | 8 (18) |
| Headache | 13 (34) | 14 (39) | 19 (40) | 13 (29) |
| Nasopharyngitis | 8 (21) | 8 (22) | 6 (12) | 10 (22) |
| Serious adverse events — no.¶ | 1 | 0 | 3 | 2 |
| Patients who completed the study and received all implants — no. (%)∥ | 34 (89) | 34 (94) | 46 (96) | 42 (93) |
Plus-minus values are means ±SD. There were no significant differences between the groups.
Body-mass index is the weight in kilograms divided by the square of the height in meters.
Race was self-reported.
In the U.S. trial, one patient in the placebo group who had an eye pigmentation abnormality was excluded before receiving the first implant, and two other patients discontinued the study early owing to medical reasons that were unrelated to the study drug. In the European Union trial, a physician decided to withdraw one patient from the study because of worsening of preexisting severe headaches.
Serious adverse events in the afamelanotide groups were subcapital humerus fracture with uncomplicated repair, herniated disk, abdominal pain, and benign compound nevus. Serious adverse events in the placebo groups were pulmonary embolus and melanoma. All serious adverse events were deemed by the investigators not to be related to study drugs.
Patients in the European Union study received five implants, and those in the U.S. study received three implants.