rosolized pentamidine 300 mg once monthly (n = 186). The majority of subjects were white (79%), male (92%), and were primary prophylaxis patients at enrollment (58%); the mean age was 38 years. Median follow-up was 11.3 months. The results of the PCP event rates appear in Table 7. Mortality rates were similar among the groups.
Table 7. Confirmed or Presumed/Probable PCP Events (As-Treated Analysis)a
aThose events occurring during or within 30 days of stopping assigned treatment.
bRelative risk <1 favors MEPRON and values >1 favor comparator. Trial results did not show superiority of MEPRON to the comparator.
cThe confidence level of the interval for the dapsone comparative trial was 95% and for the pentamidine comparative trial was 97.5%.
An analysis of all PCP events (intent-to-treat analysis) for both trials showed results similar to those shown in Table 7.
14.2 Treatment of PCP
The indication for treatment of mild‑to‑moderate PCP is based on the results of two efficacy trials: a randomized, double‑blind trial comparing MEPRON tablets with TMP‑SMX in subjects with HIV/AIDS and mild‑to‑moderate PCP (defined in the protocol as [(A‑a)DO2] ≤45 mm Hg and PaO2 ≥60 mm Hg on room air) and a randomized open-label trial comparing MEPRON tablets with IV pentamidine isethionate in subjects with mild‑to‑moderate PCP who could not tolerate trimethoprim or sulfa antimicrobials. Both trials were conducted with the tablet formulation using 750 mg three times daily. Results from these efficacy trials established a relationship between plasma atovaquone concentration and successful outcome. Successful outcome was defined as improvement in clinical and respiratory measures persisting at least 4 weeks after cessation of therapy. Comparative pharmacokinetic trials of the suspension and tablet formulations established the currently recommended suspension dose of 750 mg twice daily [see Clinical Pharmacology (12.3)].
TMP‑SMX Comparative Trial
This double‑blind, randomized trial compared the safety and efficacy of MEPRON tablets with that of TMP‑SMX for the treatment of subjects with HIV/AIDS and histologically confirmed PCP. Only subjects with mild‑to‑moderate PCP were eligible for enrollment.
A total of 408 subjects were enrolled into the trial. The majority of subjects were white (66%) and male (95%); the mean age was 36 years. Eighty‑six subjects without histologic confirmation of PCP were excluded from the efficacy analyses. Of the 322 subjects with histologically confirmed PCP, 160 were randomized to receive 750 mg MEPRON (three 250-mg tablets) 3 times daily for 21 days and 162 were randomized to receive 320 mg TMP plus 1,600 mg SMX 3 times daily for 21 days. Therapy success was defined as improvement in clinical and respiratory measures persisting at least 4 weeks after cessation of therapy. Improvement in clinical and respiratory measures was assessed using a composite of parameters that included oral body temperature, respiratory rate, severity scores for cough, dyspnea, and chest pain/tightness. Therapy failures included lack of response, treatment discontinuation due to an adverse experience, and uneva luable.
There was a significant difference (P = 0.03) in mortality rates between the treatment groups favoring TMP-SMX. Among the 322 subjects with confirmed PCP, 13 of 160 (8%) subjects treated with MEPRON and 4 of 162 (2.5%) subjects recei |
