Shionogi, Inc and Purdue Pharma, L.P. today announced the publication of a study known as COMPOSE-3. The study is the first to investigate a peripherally-acting mu-opioid receptor antagonist (PAMORA) over the course of 52 weeks in a randomized, placebo-controlled and double-blind manner. The study was published online ahead of print in PAIN, the journal of the International Association for the Study of Pain.
"The publication of the results of COMPOSE-3 in PAIN is significant as the study provides additional important information regarding the safety and tolerability of Symproic over the course of 52 weeks for adults with OIC and chronic non-cancer pain," said Dr. Tsutae "Den" Nagata, Chief Medical Officer, Shionogi.
Study Design and Results
This randomized, double-blind, placebo-controlled, parallel-group, Phase 3 clinical trial (COMPOSE-3) evaluated the long-term safety and tolerability of once-daily oral Symproic 0.2 mg for 52 weeks in patients with chronic non-cancer pain, on a stable opioid therapy, and who could be on a routine laxative regimen but still had OIC.
In the study, 2,414 patients were screened. Patients had to be aged 18 to 80, have had chronic non-cancer pain for at least 3 months, were receiving a stable daily dose of opioids (greater than or equal to 30 mg oral morphine equivalents) for at least one month prior to screening, and had self-reported OIC. From the patients screened, 1,246 eligible patients with confirmed OIC were randomized 1:1 to receive once-daily oral Symproic 0.2 mg (n=623) or placebo (n=623) for 52 weeks.
The primary endpoint was summary measures of treatment-emergent adverse events (TEAEs). Similar proportions of patients taking Symproic and placebo experienced TEAEs (Symproic, 68.4% (n=425) vs placebo 72.1% (n=446); difference: −3.6% [95% CI: −8.7-1.5]) and TEAEs leading to study discontinuation (Symproic 6.3% vs placebo 5.8%; difference: 0.5% [95% CI: –2.2-3.1]). Diarrhea was the most common TEAE in the Symproic group (11%) and was reported more frequently vs placebo (5.3%; difference: 5.6% [95% CI: 2.6-8.6]). A greater proportion of patients treated with Symproic vs placebo reported other gastrointestinal-related treatment-emergent adverse events, including abdominal pain (8.2% vs 3.1%) and vomiting (6.0% vs 3.1%). The incidences of treatment-related serious adverse events (Symproic, 0.5% vs placebo, 1.0%; difference: −0.5% [95% CI: −1.4-0.5]) and serious TEAEs leading to study discontinuation (Symproic, 1.1% vs placebo, 1.9%; difference: −0.8% [95% CI: −2.2-0.6]) were consistent between treatment groups.
The 52-week safety study included efficacy endpoints as well, which were secondary. One of these endpoints, frequency of bowel movements, was also assessed in the primary endpoint of the two 12-week pivotal studies, and the results were consistent.
"We are pleased to share with the scientific community the publication of the first 52-week double-blind study evaluating the safety of a PAMORA in adult patients with OIC and chronic non-cancer pain," said Monica Kwarcinski, PharmD, Head of Medical Affairs, Purdue Pharma L.P. "In collaboration with our partners at Shionogi, we are committed to supporting adult patients who live with OIC and chronic non-cancer pain and the physicians who treat them."
Symproic, a once-daily oral PAMORA medication approved by the U.S. Food and Drug Administration (FDA) in March 2017, is indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Symproic is available as a 0.2 mg once-daily oral tablet and may be taken at any time of day, with or without food, and with or without laxatives. Alteration of analgesic dosing regimen prior to initiating Symproic is not required. Patients receiving opioids for less than 4 weeks may be less responsive to Symproic. Treatment with Symproic should be discontinued if treatment with the opioid medicine is also discontinued.
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