Clinical Trials Experience
The safety profile of SELZENTRY is primarily based on 840 HIV-infected subjects
who received at least one dose of SELZENTRY during two Phase 3 trials. A total of
426 of these subjects received the indicated twice daily dosing regimen.
Assessment of treatment-emergent adverse events is based on the pooled data from
two studies in subjects with CCR5-tropic HIV-1 (A4001027 and A4001028). The median
duration of maraviroc therapy for subjects in these studies was 34 weeks, with the
total exposure on SELZENTRY twice daily at 267 patient-years versus 99 patient-years
on placebo. The population was 89% male and 84% white, with mean age of 46 years
(range 17-75 years). Subjects received dose equivalents of 300 mg maraviroc once
or twice daily.
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates
in the clinical trials of another drug and may not reflect the rates observed in
practice.
The most common adverse events reported with SELZENTRY twice daily therapy with
frequency rates higher than placebo, regardless of causality, were cough, pyrexia,
upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain
and dizziness. Additional adverse events that occurred with once daily dosing at
a higher rate than both placebo and twice daily dosing were diarrhea, edema, influenza,
esophageal candidiasis, sleep disorders, rhinitis, parasomnias, and urinary abnormalities.
In these two studies, the rates of discontinuation due to adverse events were 3.8%
in subjects receiving SELZENTRY twice daily + optimized background therapy (OBT)
compared to 3.8% in those receiving placebo + OBT. Most of the adverse events reported
were judged to be mild to moderate in severity. The data described below occurred
with SELZENTRY twice daily dosing.
The total number of subjects reporting infections were 214 (50.2%) and 80 (38.3%)
in the SELZENTRY twice daily and placebo groups, respectively. Correcting for the
longer duration of exposure on SELZENTRY compared to placebo, the exposure-adjusted
frequency (rate per 100 subject-years) of these events was similar: 126 and 118
for SELZENTRY and placebo, respectively.
Dizziness or postural dizziness occurred in 8.2% and 7.7% on SELZENTRY and placebo,
respectively, with 2 subjects (0.5%) on SELZENTRY discontinuing therapy (1 due to
syncope, 1 due to orthostatic hypotension) versus 1 subject on placebo (0.5%) discontinuing
therapy due to dizziness.
Treatment-emergent adverse events, regardless of causality, from A4001027 and A4001028
are summarized in Table 2. Selected events occurring at ?2% of subjects and at a
numerically higher rate in subjects treated with SELZENTRY are included; events
that occurred at a higher rate on placebo are not displayed.
Table 2: Percentage of Subjects with Selected Treatment-Emergent Adverse Events (All
Causality) (>2% on SELZENTRY and at a higher rate compared to placebo)
Studies (Pooled Analysis, up to 48 weeks)
* 300 mg dose equivalent
**PYE=patient years of exposure
***MedDRA High Level Terms are shown in order to group
related terms for all disorders except Infections and Infestations,which shows MedDRA
Preferred Terms with the following related terms grouped:
Bronchitis: bronchitis, acute bronchitis, bacterial bronchitis
Herpes simplex infection: Herpes simplex, Herpes virus, Herpes ophthalmic,
proctitis Herpes
Influenza: Influenza, influenza-like illness
Pneumonia: Pneumonia, lobar pneumonia, pneumonia bacterial, bronchopneumonia
Sinusitis: sinusitis, acute sinusitis, chronic sinusitis, sinobronchitis
Upper Respiratory Infection: upper respiratory tract infection, laryngitis,
laryngopharyngitis, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis,
viral respiratory tract infection
Less Common Adverse Events
The following adverse events [defined as always serious by MedDRA-Preferred -(Critical)-
Terms] occurred in <2% of SELZENTRY-treated patients. These events have been
included because of their seriousness and either increased frequency on SELZENTRY
or are potential risks due to the mechanism of action. Events attributed to the
patient’s underlying HIV infection are not listed.
Cardiac Disorders: unstable angina, acute cardiac failure, coronary artery
disease, coronary artery occlusion, myocardial infarction, myocardial ischemia
Hepatobiliary Disorders: hepatic cirrhosis, hepatic failure, cholestatic
jaundice
Infections and Infestations: Clostridium difficile colitis, viral
meningitis, pneumonia, septic shock
Musculoskeletal and Connective Tissue Disorders: myositis, osteonecrosis,
rhabdomyolysis, blood CK increased
Neoplasms benign, Malignant and Unspecified (including Cysts and Polyps):
abdominal neoplasm, anal cancer, basal cell carcinoma, Bowen’s disease, cholangiocarcinoma,
lymphoma, metastases to liver, esophageal carcinoma, squamous cell carcinoma, squamous
cell carcinoma of skin, tongue neoplasm (malignant stage unspecified)
Nervous System Disorders: cerebrovascular accident
Laboratory Abnormalities
Table 3 shows the treatment-emergent Grade 3-4 laboratory abnormalities that occurred
in >2% of patients receiving SELZENTRY.
Table 3: Maximum Shift in Laboratory Test Values (Without Regard to Baseline)
Incidence ≥2% of Grade 3-4 Abnormalities (ACTG Criteria)
A4001027 and A4001028 (Pooled Analysis, Up to 48 Weeks)
