Active Ingredients: Gabapentin
Pharmacokinetics The pharmacokinetics of oral gabapentin enacarbil have been evaluated in healthy volunteers, patients with RLS or postherpetic neuralgia, and patients with renal impairment.Leading manufacturers understand that consumer interest industries, co-innovating to responsibly meet consumer.
Several linear and nonlinear candidate models were tested, using the data from these studies.
The E max model best described the dose—exposure relationship for gabapentin, and the power model was the most suitable for gabapentin enacarbil.
Simulations confirmed that these models accurately reflected the distribution of the respective data.
The results of ten trials and three meta-analyses have been published in the literature. Eight of these studies were double-blind, placebo-controlled randomized trials.
The study characteristics, primary endpoints, and results of these trials are summarized in Table 1. Phase II studies XP 021 The efficacy of gabapentin enacarbil in patients with moderate to severe primary RLS was evaluated during a 2-week period in XP 021, 50 a randomized, double-blind, placebo-controlled, crossover trial.
The secondary endpoints were patient- and investigator-rated clinical global impression-improvement CGI-I, subjective measures of sleep, parameters for the suggested immobilization test and the polysomnography.
Patients treated with gabapentin enacarbil showed improvement in the patient-rated CGI-I, time in RLS symptoms on 24-hour diaries, and the subject-rated postsleep questionnaire PSQ, including overall quality of sleep, number of hours awake per night resulting from RLS symptoms, and number of awakenings per night resulting from RLS symptoms an index of sleep fragmentation compared with placebo.
XP 045 The efficacy of gabapentin enacarbil 1,200 mg and 600 mg was assessed in 95 patients with moderate to severe primary RLS in XP 045, 51 a 14-day, double-blind, randomized, placebo-controlled trial. XP 081 XP 081, 43 a randomized, 12-week, double-blind, placebo-controlled, parallel-group clinical trial was conducted to assess the pharmacokinetics and efficacy of gabapentin enacarbil in patients with moderate to severe primary RLS.
Exposure to gabapentin was proportional to gabapentin enacarbil dose. The results indicated that all four dose levels of gabapentin enacarbil provided efficacious drug exposure because all doses resulted in numerically greater relief of symptoms in subjects with RLS compared with placebo.
The coprimary outcome measures were the mean change in IRLS total score from baseline to week 12 and the proportion of responders on the CGI-I scale at week 12. On the investigator-rated CGI-I, significantly more gabapentin enacarbil-treated patients responded than patients treated with placebo 76.
Subjects treated with gabapentin enacarbil also experienced a significant increase in RLS quality-of-life scores compared with placebo-treated patients 21.
Significantly more subjects treated with gabapentin enacarbil 600 mg 72. PSQ revealed that gabapentin enacarbil at both doses significantly improved overall quality of sleep and resulted in improved ability to function, fewer nights with RLS symptoms, fewer awakenings and fewer hours awake per night compared with placebo.
A statistically significant lower percentage of gabapentin enacarbil-treated subjects relapsed during the double-blind phase compared with placebo 9.
XP 055 The long-term efficacy of gabapentin enacarbil in patients with moderate to severe primary RLS was evaluated in XP 055, 55 an open-label, multicenter, 52-week extension study that enrolled 573 participants who completed one of four short-term parent trials XP 052, XP 053, XP 081, XP 063.
All subjects received gabapentin enacarbil at 5 pm with food for up to 52 weeks. At week 52 LOCF, the mean change from parent study baseline 23.