Study of Naldemedine in the Treatment of Opioid-induced Constipation in Subjects with Non-malignant Chronic Pain Receiving Opioid Therapy

• Conditions: Opioid-induced Constipation in Subjects with Non-malignant Chronic Pain Receiving Opioid Therapy; MedDRA version: 18.0Level: LLTClassification code 10071128Term: Opioid induced constipationSystem Organ Class: 100000004856; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2013-002948-91-PL
• Lead Sponsor: Shionogi Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-05-08
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 540

Inclusion Criteria

1. Subjects aged 18 to 80 years inclusive at the time of informed consent
2. Subjects must have non-malignant chronic pain treated with opioids for at least 3 months and must have OIC
3. Subjects must be treated with a stable opioid regimen at a total daily dose on average of = 30 mg equivalents of oral morphine sulfate for at least 1 month prior to Screening
4. Subjects must not be currently using laxatives or must be willing to discontinue laxative use (e.g., stool softener, bulking agents, gastrointestinal tract stimulants/prokinetic agents, suppositories, enemas or other medications/agents used to treat constipation) at the time of Screening and must be willing to use only the rescue laxatives provided throughout the study duration
5. Subjects must meet the following 3 criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary collected via eDiary over a 14 consecutive day qualifying period during the 28 day Screening Period:
a. No more than 4 SBMs total over the 14 consecutive day qualifying period. In addition, no more than 3 SBMs in a given week of the qualifying period.
b. Experience one or more of the following bowel symptoms in 25% or more of BMs:
1.Presence of straining
2.Lumpy or hard stools
3.Sensation of incomplete evacuation
4.Sensation of anorectal obstruction/blockage
c.Subjects must have at least 78% compliance with daily completion of eDiary entries (i.e., make 11 of 14 diary completions) during the 14 consecutive day qualification period
6. Males will be either sterile for 6 months prior to Screening (e.g., vasectomy) or agree to use an approved method of contraception (use of a condom with spermicide from the start of the Screening visit until 28 days after the last dose of IMP)
7. Females must be non-pregnant, non-lactating, and either postmenopausal (defined as cessation of regular menstrual periods for at least 1 year if = 50 years old or 2 years if < 50 years old with follicle-stimulating hormone (FSH) confirmation), surgically sterile by hysterectomy, bilateral oophorectomy or agree to use a highly effective (with failure rates < 1%/year) technique of birth control from Screening visit until 28 days after the last dose of IMP, such as:
a.hormonal implants, injectables, combined oral contraceptives
b.intrauterine contraceptive devices
c.barrier method of contraception (condom or occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository or condom in combination with tubal ligation)
8. Subjects who are not currently sexually active (abstinent) must agree to use one of the above-mentioned methods if they become sexually active while participating in the study
9. Females of child bearing potential must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at Visit 2 (Day 1), prior to dosing
10. Able to understand and willing to sign an informed consent form prior to Screening, and comply with all study procedures and requirements

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 290

Exclusion Criteria

1. Evidence of significant structural abnormalities of the gastrointestinal tract (GI)
a.history of bowel obstructions, strictures
b.history of bowel surgery such as bowel resection or bariatric surgeries
2. Evidence of active medical diseases affecting bowel transit such as ileus, uncontrolled hypothyroidism, irritable bowel syndrome (IBS), inflammatory bowel disease (ulcerative colitis, Crohn’s disease, diverticulitis), fecal incontinence
3. History or presence of pelvic disorders that may be a cause of constipation
4. Surgery (except for minor procedures) within 60 days of Screening, or planned surgery during study treatment that would influence pain or bowel function or preclude completion of the study
5. History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation (e.g., mechanical gastrointestinal obstruction)
6. Severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation. This includes subject who have reported no bowel movements for 7 consecutive days prior to and during the Screening Period
7. Subjects who have never taken laxatives for the treatment of OIC
8. Initiation of a new bowel regimen or prokinetic agent, or significant change in diet supplement use, or exercise regimens within 28 days of the Screening visit
9. History of active treatment for cancer within the last 2 years (except for basal cell or squamous cell carcinoma of the skin that have been successfully resected or tamoxifen [Nolvadex®] and raloxifene [Evista®] when being used for prevention of breast cancer)
10. Abnormal laboratory tests at Screening:
a.>2 × upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
b.>1.5 × ULN for total bilirubin
c.>1.5 × ULN for serum creatinine
11. Subjects with a significant comorbid medical condition(s) to the extent that study participation may not be in the subject’s best interest or that may interfere with study compliance/completion. Comorbid conditions may include cardiovascular, respiratory, hepatic, renal, endocrine dysfunction, or a history of human immunodeficiency (HIV)
12. Subjects who have significant cardiovascular (CV) risk such as presence or suspected presence of unstable coronary artery disease, myocardial infarction (MI), stroke or transient ischemic attack (TIA) within 3 months of Screening
13. Presence of any medical or psychiatric condition that, in the opinion of the Investigator, may compromise the ability of the subject to understand and comply with the study protocol or provide informed consent to participate in the study
14. Positive result for serologic test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or active hepatitis A virus (HAV)
15. Current use of any prohibited medication listed in Section 6.2.5 including opioid antagonists, partial agonists or mixed agonist/antagonists
16. Any history of illegal drug use in the last 2 years, documented misuse of prescribed medications or a positive urine drug screen (unless the positive drug substance has been prescribed)
17. Any allergic reaction to opioids or known or suspected hypersensitivity to naltrexone hydrochloride, methylnaltrexone bromide, naloxone hydrochloride, alvimopan or any other opioid antagonist
18. Treatment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified