Constipation and bowel cleansers:
Indications for: MOTEGRITY
Chronic idiopathic constipation (CIC) in adults.
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.
≥17yrs: 2mg once daily. Severe renal impairment (CrCl <30mL/min): 1mg once daily.
<17yrs: not established.
Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, or severe inflammatory conditions of the intestinal tract (eg, Crohn’s disease, ulcerative colitis, toxic megacolon/megarectum).
Monitor for new onset or worsening of depression or the emergence of suicidal thoughts/behaviors; discontinue if occurs. Elderly: adjust dose based on renal function. ESRD requiring dialysis: not recommended. Pregnancy. Nursing mothers.
Selective 5-HT4 receptor agonist.
Headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, fatigue; suicidal ideation/behavior.
Renal (84.2%), fecal (13.3%).
Generic Drug Availability: