The COMPOSE-4 trial was specifically designed to evaluate the efficacy and safety of naldemedine, a peripherally acting μ-opioid receptor antagonist, in alleviating OIC in this vulnerable population.

Study design

The main goal of COMPOSE-4 was to demonstrate the efficacy of naldemedine compared to placebo in treating OIC in adults with cancer pain, after a 14-day course of treatment. COMPOSE-4 was a multicenter, phase 3, double-blind, randomized, parallel-group trial conducted over two weeks. It involved 193 cancer patients who were on a stable daily dose of opioids and experiencing significant constipation as a result. Participants were randomized in a 1:1 ratio to receive either 0.2 mg of naldemedine or a placebo tablet once per day.

The inclusion criteria targeted adult cancer patients aged 20 years and older who had been receiving a stable dose of opioids for at least 2 weeks prior to randomization. These patients had a history of five or fewer spontaneous bowel movements over the 14 days before randomization, with significant constipation symptoms such as straining, incomplete evacuation, or hard stools.

Patients were required to continue their regular laxative regimen without any changes throughout the screening and treatment phases. However, if an adverse event, such as diarrhea, significantly affected the patient's quality of life, the investigator could permit a temporary halt or reduction in the laxative dosage. Additionally, patients were allowed to use rescue laxatives as necessary, except for the 24 hours before and after administering the initial dose of the study medication.

Efficacy outcomes

The primary endpoint of the trial was the proportion of patients achieving ≥3 spontaneous bowel movements (SBMs) per week with an increase of at least 1 SBM per week compared to baseline. This measure directly assessed the effectiveness of naldemedine in enhancing bowel function over the treatment period.

A significant difference was observed in the proportion of SBM responders between the naldemedine and placebo groups. Approximately 71.1% of patients in the naldemedine group met the primary endpoint compared to only 34.4% in the placebo group, with a p-value of <0.0001.

Image adapted by Viatris from Katakami et al (2017)

Safety and tolerability

Safety was a critical component of the trial, given the vulnerable condition of the patient population. The safety assessments focused on the frequency of adverse events, particularly gastrointestinal disorders, which were the most pertinent to the treatment.

• Overall incidence: Adverse events were reported in 44.3% of patients in the naldemedine group compared to 26% in the placebo group. The higher incidence in the naldemedine group was anticipated due to its pharmacological action on the gastrointestinal system.
• Discontinuations due to adverse events: A small percentage of patients discontinued treatment due to adverse events, with 9.3% in the naldemedine group and 1% in the placebo group. This reflected the generally well-tolerated nature of the treatment despite the higher incidence of adverse events.

Image adapted by Viatris from Katakami et al (2017)

Clinical implications

The COMPOSE-4 trial demonstrated that naldemedine effectively and rapidly improves bowel function in cancer patients suffering from OIC. The substantial difference in response rates between the naldemedine and placebo groups demonstrate the potential of naldemedine to provide significant relief from constipation.

For oncologists and palliative care professionals, the results from COMPOSE-4 offer a promising therapeutic option for managing OIC in cancer patients. Naldemedine may provide relief of the OIC that can help patients continue their prescribed opioid regimen effectively.

Conclusion

COMPOSE-4 adds valuable knowledge to the field of pain management in oncology, demonstrating that naldemedine is an effective and rapid treatment for OIC in cancer patients. This trial shows the potential for naldemedine to address acute constipation issues, facilitating better overall patient management in cancer pain therapy.

For more information on uncommon or rare side effects, see the Summary of Product Characteristics.

NO-RIZM-2024-00003 | 11-2024