MOTEGRITY Rx

The efficacy of Motegrity for the treatment of CIC was evaluated in 6 double-blind, placebo-controlled, randomized, multicenter clinical trials in 2484 adult patients (Studies 1 to 6). Studies 1 through 5 were 12-week treatment duration and Study 6 included 24 weeks of treatment. Patients less than 65 years were dosed with Motegrity 2 mg once daily. In Studies 2 and 6, the geriatric patients started on Motegrity 1 mg once daily and, if necessary, the dose was increased to 2 mg after 2 or 4 weeks of treatment in the event of insufficient response at 1 mg; of these patients 81% increased to 2 mg. The mean duration of constipation was 16±15 years with 28% of patients having chronic constipation for ≥20 years.

Eligible patients required a history of chronic constipation defined as having fewer than 3 spontaneous bowel movements (SBMs) per week that resulted in a feeling of complete evacuation (complete, spontaneous bowel movement [CSBM]), and ≥1 of the following symptoms for >25% of bowel movements in the preceding 3 months, with symptoms onset >6 months prior to screening:

• Lumpy or hard stools
• Sensation of incomplete evacuation
• Straining at defecation

Patients who never had SBMs were eligible. In Study 1, eligibility also included sensation of ano-rectal obstruction or blockade or the need for digital manipulation in >25% of bowel movements. In all studies, patients were excluded if constipation was due to secondary causes or suspected to be drug-induced.

Efficacy was assessed using information provided by patients in a daily diary.

Primary Efficacy Results

For the primary efficacy endpoint, a responder was defined as a patient with an average of ≥3 CSBMs per week, over the 12-week treatment period. In the Intent-to-Treat [ITT] population in the 6 trials, 1237 received Motegrity 1 or 2 mg and 1247 received placebo. 

• Study 1: Treatment difference: 23% (95% CI, 16-30); P <0.001
• Study 2: Treatment difference: 20% (95% CI, 11-29); P <0.001
• Study 3: Treatment difference: 10% (95% CI, 4-16); P =0.002
• Study 4: Treatment difference: 16% (95% CI, 8-24); P <0.001
• Study 5: Treatment difference: 12% (95% CI, 4-19); P <0.001
• Study 6: Treatment difference: 5% (95% CI, -4, 14); P =0.341

Improvement in the frequency of CSBMs/week was seen in all of the studies, as early as week 1 and was maintained through week 12.

Across the 6 studies, the median time to first CSBM after dosing of Motegrity on day 1 ranged from 1.4–4.7 days vs 9.1–20.6 days in the placebo group. The median time to first SBM after dosing on day 1 ranged from 0.1–0.4 days in the Motegrity group vs 1.0–1.6 days in the placebo group.