Abstract
Background
Factors including frailty and multimorbidity can affect candidaemia and/or invasive candidiasis (C/IC) treatment in older people.1 The current analysis explored data from C/IC patients aged ≥65 years who were treated with rezafungin or caspofungin in the STRIVE (Phase 2: NCT02734862) and ReSTORE (Phase 3: NCT03667690) clinical trials.2,3
Methods
STRIVE and ReSTORE were double-blind, randomized studies. Adults with C/IC, diagnosed by systemic signs and mycological confirmation, received rezafungin once-weekly (Week 1: 400 mg; Weeks 2–4: 200 mg) or once-daily caspofungin (Day 1: 70 mg; Days 2–28: 50 mg) by IV injection for ≥14 days (≤4 weeks). Post hoc analysis examined pooled STRIVE/ReSTORE data for subjects aged ≥65 years. Safety outcomes included treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) in subjects who received ≥1 dose of study drug (safety population). Day 30 all-cause mortality (ACM) and mycological response at Days 5 and 14 were examined for the modified intention-to-treat (mITT) population (subjects with mycological C/IC diagnosis within 96 h of randomization who received ≥1 study drug dose).
Results
The safety population included 132 subjects (rezafungin arm: 64; caspofungin arm: 68). The mITT population included 120 subjects (rezafungin arm: 57; caspofungin arm: 63). The most common TEAEs with rezafungin were hypokalaemia, diarrhoea, vomiting and anaemia (Table 1). Eight subjects reported rezafungin-related TEAEs and seven had caspofungin-related TEAEs. SAEs comprised one case each of first degree atrioventricular block (rezafungin arm) and acute liver injury (caspofungin arm). Day 30 ACM rate was 14.0% (rezafungin arm) and 31.7% (caspofungin arm). The between-group difference (95% CI) was -17.6 (−32.5, −2.8). Day 5 mycological response was 78.9% (rezafungin arm) and 58.7% (caspofungin arm; difference [95% CI]: 19.3 [3.3, 35.2]; Figure 1).
Conclusions
Integrated analysis of pooled STRIVE/ReSTORE study data revealed similar incidence of drug-related TEAEs and SAEs in patients aged ≥65 years treated with rezafungin or caspofungin. Further analyses are required to understand underlying factors influencing between-group differences regarding treatment outcomes.
Safety data for candidaemia/invasive candidiasis patients aged ≥65 years treated with rezafungin (400 mg/200 mg) or caspofungin (70 mg/50 mg) (safety population)
| Rezafungin (400/200 mg) (N=64), n (%) | Caspofungin (70/50 mg) (N=68), n (%) | |
|---|---|---|
| Subjects with at least 1 TEAE | 59 (92.2) | 62 (91.2) |
| Subjects with TEAEs leading to study discontinuation | 7 (10.9) | 19 (27.9) |
| Subjects with at least 1 drug-related TEAE | 8 (12.5) | 7 (10.3) |
| Subjects with at least 1 SAE | 37 (57.8) | 38 (55.9) |
| Subjects with at least 1 drug-related SAE | 1 (1.6) | 1 (1.6) |
| TEAEs affecting at least 10% of safety population | ||
| Hypokalaemia | 11 (17.2) | 7 (10.3) |
| Diarrhoea | 10 (15.6) | 9 (13.2) |
| Vomiting | 8 (12.5) | 2 (2.9) |
| Anaemia | 7 (10.9) | 5 (7.4) |
| Septic shock | 6 (9.4) | 8 (11.8) |
| Acute kidney injury | 4 (6.3) | 8 (11.8) |
| Urinary tract infection | 1 (1.6) | 7 (10.3) |
The safety population included all subjects who had received ≥1 dose of study drug.
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Details
1 University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Internal Medicine, Excellence Center for Medical Mycology (ECMM) , Cologne , Germany
2 University of California Davis Medical Center , Sacramento, CA , USA
3 Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona , Barcelona , Spain
4 Radboud University Medical Center , Nijmegen , The Netherlands
5 Washington University , St Louis, MO , USA
6 Augusta University , Augusta, GA , USA
7 Brugman University Hospital , Brussels , Belgium
8 University of Genoa , Genoa , Italy
9 Mercury Street Medical , Butte, MT , USA
10 PSI-CRO , Durham, NC , USA
11 Cidara Therapeutics Inc. , San Diego, CA , USA
12 University of Alabama at Birmingham , Birmingham, AL , USA