Table 3.
Adverse events.
| Patients | Week 0–12: placebo-controlled period |
Week 12–24: open-label period |
||||
|---|---|---|---|---|---|---|
| Roflumilast n = 23 |
Placebo n = 23 |
Roflumilast n = 46 |
||||
| n | EAIR/100 patient years | n | EAIR/100 patient years | n | EAIR/100 patient years | |
| Adverse events (AEs) | ||||||
| ≥1 drug-related | 20 (87) | 904 | 14 (61) | 437 | 30 (65) | 787 |
| ≥1 non-drug related | 14 (61) | 414 | 13 (57) | 364 | 23 (50) | 452 |
| Serious AEs (SAEs) | ||||||
| ≥1 drug-related | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| ≥1 non-drug related | 0 (0) | 0 | 0 (0) | 0 | 1 (3)a | 11 |
| ≥1 suspected unexpected serious adverse reaction (SUSAR) | 0 (0) | 0 | 0 (0) | 0 | 0 (0.0) | 0 |
| AEs leading to drug discontinuation | 1 (4)b | 19 | 1 (4)c | 19 | 1 (3)d | 11 |
| Drug-related AEs reported by ≥5 patients in any treatment group in any study phase, n (%) | ||||||
| Weight loss | 19 (83) | 800 | 9 (39) | 229 | 32 (70) | 1128 |
| Reduced appetite | 14 (61) | 434 | 10 (44) | 256 | 21 (46) | 386 |
| Nausea | 12 (52) | 354 | 6 (26) | 131 | 11 (24) | 150 |
| Headache | 11 (48) | 301 | 6 (26) | 134 | 8 (17) | 100 |
| Abdominal pain | 9 (39) | 226 | 6 (26) | 137 | 7 (15) | 86 |
| Insomnia | 9 (39) | 227 | 8 (35) | 188 | 12 (26) | 166 |
| Diarrhea | 7 (30) | 160 | 6 (26) | 136 | 8 (17) | 103 |
| Vertigo | 5 (22) | 110 | 2 (9) | 40 | 4 (9) | 46 |
| Back pain | 3 (13) | 62 | 3 (13) | 64 | 2 (4) | 23 |
| Upper respiratory tract infection | 3 (13) | 62 | 0 (0) | 0 | 5 (11) | 61 |
| Malaise | 2 (9) | 40 | 2 (9) | 41 | 4 (9) | 46 |
| Constipation | 2 (9) | 40 | 0 (0) | 0 | 0 (0) | 0 |
| Nervousness | 2 (9) | 40 | 2 (9) | 40 | 2 (4) | 23 |
| Fatigue | 2 (9) | 40 | 3 (13) | 63 | 4 (9) | 46 |
| Myalgia | 1 (4) | 20 | 3 (13) | 62 | 1 (2) | 11 |
| Palpitations | 1 (4) | 20 | 2 (9) | 40 | 2 (4) | 22 |
| Tremor | 1 (4) | 20 | 2 (9) | 39 | 1 (2) | 11 |
| Tiredness | 0 (0) | 0 | 2 (9) | 40 | 1 (2) | 11 |
| Vomiting | 0 (0) | 0 | 0 (0) | 0 | 3 (7) | 35 |
| Non-drug related AEs reported by ≥5 patients in any treatment group in any study phase, n (%) | ||||||
| Upper airway infection | 3 (13) | 64 | 1 (4) | 20 | 7 (15) | 88 |
| Insomnia | 2 (9) | 41 | 1 (4) | 20 | 0 (0) | 0 |
| Stress | 2 (9) | 40 | 0 (0) | 0 | 2 (4) | 23 |
| Covid-19 infection | 2 (9) | 40 | 1 (4) | 20 | 2 (4) | 22 |
| Selected laboratory abnormalities | ||||||
| ALT >3 × ULN, U/L | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| AST >3 × ULN, U/L | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| Bilirubin >1.8 × ULN, μmol/L | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| HbA1c >75 mmol/mol | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| Total cholesterol >7.8 mmol/L | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| Triglycerides >3.4 mmol/L | 1 (4) | 19 | 1 (4) | 20 | 2 (4) | 11 |
| Lymphocytes <0.8 × 109/L | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
| Neutrophils <1 × 109/L | 0 (0) | 0 | 0 (0) | 0 | 0 (0) | 0 |
Multiple occurrences of an identical event in the same patient figure at the first registration time point within each treatment period. Weight loss is defined by >1 kg.
AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; EAIR, exposure-adjusted incidence rate; HbA1c, glycated hemoglobin; SAE, serious adverse event; SUSAR, serious unexpected suspected adverse reaction; ULN, upper limit of normal.
a
SAE; non-ischemic chest pain.
b
Gastrointestinal symptoms, headache, and insomnia.
c
Psychological imbalance/worsening of anxiety, nervousness, and gastrointestinal symptoms.
d
Gastrointestinal symptoms, vertigo, headache, and insomnia.