Table 4.
Summary of Specific Safety Issues, Phase III Studies
STARTMRK | BENCHMRK | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Raltegravir N=281 | Efavirenz N=282 | Raltegravir N=462; PYR=708 | Placebo N=237; PYR=244 | ||||||||||
% | % | % | Rate† | % | Rate† | ||||||||
Rash in Overall Population | |||||||||||||
All | 9.6 | 20.9 | 11.3 | 7.3 | 6.3 | 6.1 | |||||||
Drug-related‡ | 1.8 | 13.8 | 2.6 | 1.7 | 3.8 | 3.7 | |||||||
Serious | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Discontinued | 0.0 | 1.1 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Rash in Patients Who Received OBT with Darunavir | |||||||||||||
All | NA | NA | 17.4 | 10.9 | 4.8 | 3.8 | |||||||
Drug-related‡ | NA | NA | 3.9 | 2.4 | 2.9 | 2.3 | |||||||
Serious | NA | NA | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Discontinued | NA | NA | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Rash in Patients Who Received OBT without Darunavir | |||||||||||||
All | NA | NA | 6.3 | 4.2 | 7.5 | 8.8 | |||||||
Drug-related‡ | NA | NA | 1.6 | 1.1 | 4.5 | 5.3 | |||||||
Serious | NA | NA | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Discontinued | NA | NA | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Depression/Suicidality | |||||||||||||
All | 7.5 | 8.9 | 3.7 | 2.4 | 5.5 | 5.3 | |||||||
Drug-related‡ | 2.5 | 3.9 | 0.6 | 0.4 | 0.8 | 0.8 | |||||||
Serious | 0.7 | 0.7 | 0.4 | 0.3 | 0.8 | 0.8 | |||||||
Discontinued | 0.0 | 0.4 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
IRIS | |||||||||||||
All | 6.8 | 4.6 | 0.4 | 0.3 | 0.4 | 0.4 | |||||||
Drug-related‡ | 3.2 | 1.1 | 0.0 | 0.0 | 0.4 | 0.4 | |||||||
Serious | 1.8 | 0.7 | 0.4 | 0.3 | 0.0 | 0.0 | |||||||
Discontinued | 0.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Lipodystrophy | |||||||||||||
All | 0.0 | 0.7 | 5.6 | 3.7 | 3.0 | 2.9 | |||||||
Drug-related‡ | 0.0 | 0.4 | 4.8 | 3.1 | 3.0 | 2.9 | |||||||
Serious | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Discontinued | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Increased CK with Clinical Manifestations (Myopathy, Myositis, or Rhabdomyolysis) | |||||||||||||
Grade 3 or 4 CK | NA | NA | 6.7 | 4.4 | 3.4 | 3.3 | |||||||
Discontinued Due to Laboratory AE | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | |||||||
Myopathy, Myositis or Rhabdomyolysis | 0.4 | 0.0 | 0.2 | 0.1 | 0.4 | 0.4 |
PYR = Person Years at Risk.
N = Number of patients in each treatment group.
Events per 100 person-years, with person-years at risk (PYR) calculated based on the overall endpoint.
Determined by the investigator to be possibly, probably, or definitely drug related.
NA = Not Applicable.
Note: For BENCHMRK Studies Raltegravir and Placebo were administered with Optimized Background Therapy (OBT). For STARTMRK Raltegravir and Efavirenz were administered with tenofovir/ emtricitabine.