SYMPROIC® was studied in >1000 patients

Study population9,11

  • Eligible patients were receiving a stable opioid morphine equivalent daily dose of at least 30 mg for 4 weeks or more before enrollment and self-reported OIC
  • OIC was confirmed through a 2-week run-in period and was defined as no more than 4 SBMs over 14 consecutive days and fewer than 3 SBMs in a given week, with at least 25% of the SBMs associated with one or more of the following conditions: (1) straining, (2) hard or lumpy stools, (3) having a sensation of incomplete evacuation, or (4) having a sensation of anorectal obstruction/blockage. SBM was defined as a BM without rescue laxative taken within the past 24 hours
  • Patients were not using laxatives or were willing to discontinue laxatives
  • Patients were excluded if they had no BMs over the 7 consecutive days before and during the 2-week screening period; patients who had never taken laxatives were excluded, as well as those with evidence of significant structural abnormalities of the gastrointestinal tract

Two replicate, 12-week, randomized, double-blind, placebo-controlled trials9,11

Randomization

547 patients in Study 1
and 553 patients in Study 2
randomized
in a 1:1 ratio

SYMPROIC® 0.2 mg
once daily

Placebo

12-week treatment period

Bisacodyl was used as a
rescue laxative.
Study medication was administered without regard to meals.

BM=bowel movement; SBM=spontaneous bowel movement.

Patient demographics9,11

Mean Age

54 years

Sex

59% women

Mean BMI

31

Mean Baseline SBMs

1.3 and 1.2 per week (Studies 1 and 2, respectively)

Proven efficacy in two 12-week clinical trials

Endpoints are consistent with the symptoms of OIC9,11

Primary endpoint: responder rate9,11

To be considered a responder,
patients had to achieve:

3 SBMs per weekPlusChange from
baseline of 1 SBM per week

FOR

At least 9 out of 12 weeks,
INCLUDING
3 out of the last 4 weeks

Responder rates were significantly
higher with SYMPROIC®
than with placebo9,11

Primary Endpoint

More frequent SBMs with SYMPROIC®

Statistically significant increase vs placebo in frequency of SBMs per week from baseline to week 19,11

Secondary Endpoint: Frequency

CI=confidence interval; SBM=spontaneous bowel movement.
The mean baseline number of SBMs was 1.3 and 1.2 per week for Studies 1 and 2, respectively.

Change in the frequency of SBMs per week from baseline to the first week and to the last 2 weeks

Statistically significant increase vs placebo in frequency of complete SBMs (CSBMs) per week from baseline to the last 2 weeks9,11

More complete SBMs with SYMPROIC®

Statistically significant increase vs placebo per week from baseline to the last 2 weeks9,11

Secondary endpoint: Completeness

CI=confidence interval; CSBM=complete spontaneous bowel movement.
*Compared with placebo.

Change in frequency of CSBMs per week from baseline to the last 2 weeks

More SBMs without straining with SYMPROIC®

Statistically significant increase vs placebo in frequency of SBMs without straining per week from baseline to the last 2 weeks9,11

Secondary Endpoint: Straining

CI=confidence interval; SBM=spontaneous bowel movement.
*Compared with placebo.

Change in frequency of SBMs without straining per week from baseline to the last 2 weeks

Proven long-term efficacy and tolerability

Study Design12

Randomized, double-blind, placebo-controlled safety study. Patients were allowed to maintain their current laxative therapy throughout study duration.

Significant and sustained increase in bowel movements from baseline vs placebo
over 52 weeks12

BL=baseline; BM=bowel movement.
Intent-to-treat population; least squares mean ± SE. *P≤0.0001 vs placebo.
BL value for both treatment groups: 2.02 BMs per week.

INDICATION

SYMPROIC® (naldemedine) is indicated for the treatment of opioid-induced constipation (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.

Important Safety Information

Contraindications

  • Patients with known or suspected gastrointestinal (GI) obstruction and patients at increased risk of recurrent obstruction, due to the potential for GI perforation.
  • Patients with a history of a hypersensitivity reaction to naldemedine. Reactions have included bronchospasm and rash.

Warnings and Precautions

Cases of GI perforation have been reported with use of another peripherally acting opioid antagonist in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract. Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue if this symptom develops.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, increased lacrimation, hot flush/flushing, pyrexia, sneezing, feeling cold, abdominal pain, diarrhea, nausea, and vomiting have occurred in patients treated with SYMPROIC®.

Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. Take into account the overall risk-benefit profile when using SYMPROIC® in such patients. Monitor for symptoms of opioid withdrawal in such patients.

Drug Interactions

Avoid use with strong CYP3A inducers (e.g., rifampin) because they may reduce the efficacy of SYMPROIC®.

Use with moderate (e.g., fluconazole) and strong (e.g., itraconazole) CYP3A inhibitors and P-glycoprotein inhibitors (e.g., cyclosporine) may increase SYMPROIC® concentrations. Monitor for potential adverse reactions.

Avoid use of SYMPROIC® with another opioid antagonist due to the potential for additive effect and increased risk of opioid withdrawal.

Use in Specific Populations

Naldemedine crosses the placenta and may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier. SYMPROIC® should be used during pregnancy only if the potential benefit justifies the potential risk. Because of the potential for serious adverse reactions, including opioid withdrawal in breastfed infants, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Avoid use in patients with severe hepatic impairment. No dose adjustment of SYMPROIC® is required in patients with mild or moderate hepatic impairment.

Adverse Reactions

The most common adverse reactions with SYMPROIC® compared to placebo in two pooled 12-week studies were: abdominal pain (8% vs 2%), diarrhea (7% vs 2%), nausea (4% vs 2%), and gastroenteritis (2% vs 1%).

The incidence of adverse reactions of opioid withdrawal in two pooled 12-week studies was 1% (8/542) for SYMPROIC® and 1% (3/546) for placebo. In a 52-week study, the incidence was 3% (20/621) for SYMPROIC® and 1% (9/619) for placebo.

Please see Full Prescribing Information and Medication Guide for SYMPROIC®.

To report suspected Adverse Reactions, contact BioDelivery Sciences International, Inc. at 1-800-469-0261 or FDA at 1‑800‑FDA‑1088 or www.fda.gov/medwatch.