In total, 217 subjects in arm 1 completed the study.
Elevated liver enzymes reflect ALT increases (13 subjects in arm A and 16 subjects in arm B) and AST increases (8 subjects in arm A and 17 subjects in arm B).
For gastrointestinal disorders, drug-related diarrhea (13 subjects in arm A and 11 subjects in arm B) and nausea (12 subjects in arm A and 11 subjects in arm B) were most frequently reported.
The subjects in arm A participated in the metoprolol interaction and 90-day redosing evaluations, whereas subjects in arm B participated in the 60-day PA redosing evaluation.
Finally, headache occurred in 11 subjects in arm A and 12 subjects in arm B. There were no adverse events classified as severe or life-threatening.
Subjects in arm 1 of the study were asked to return in 20 days for cosmetic treatment and 40 days thereafter.
Subjects in Arm B were administered three or four PA tablets, depending on weight, on Days 1, 2, and 3. Subjects in Arm B were residents from the evening before the first administration of PA on Day 1 through the morning of Day 4; these subjects returned for ambulatory clinic visits on Days 5, 6, 8, 15, 22, 29, 36, and 43.
Including the replacement subjects, a total of 26 subjects were enrolled in arm A and 30 subjects in arm B. Overall, 12 of the 56 subjects were enrolled into the study as replacements, with 4 such subjects randomized into arm A and 8 into arm B. The timing and reasons for subject discontinuation from the study are summarized in Table 1.
In order to examine a second dose escalation strategy, subjects in Arm III will have their lithium dose increased twice weekly depending upon the effectiveness and tolerability of lithium in this cohort.
Subjects in Arm A were residents in the clinical research unit starting the evening before the first administration of ritonavir on the morning of Day 1 through the last administration of ritonavir on Day 17; these subjects returned for ambulatory clinic visits on Days 22, 29, 36, 43, and 50.
