A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation Estudio multicéntrico, aleatorizado, en doble ciego, controlado con placebo y de grupos paralelos, de MOA-728 subcutánea para el tratamiento del estreñimiento inducido por opiáceos

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2008-005961-77-ES
• Date of registration: 20/02/2009
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc.
• Public title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation Estudio multicéntrico, aleatorizado, en doble ciego, controlado con placebo y de grupos paralelos, de MOA-728 subcutánea para el tratamiento del estreñimiento inducido por opiáceos
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation Estudio multicéntrico, aleatorizado, en doble ciego, controlado con placebo y de grupos paralelos, de MOA-728 subcutánea para el tratamiento del estreñimiento inducido por opiáceos
• Date of first enrolment: 06/05/2009
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005961-77
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects aged 18 years or older.
2. Subjects weighing ? 40 kg.
3. A history of pain with documentation of a nonmalignant condition underlying the pain of at least 2 month?s duration before the screening visit.
4. Taking oral, transdermal, intravenous, or SC opioids for at least 1 month and receiving a daily dose ? 50 mg of oral morphine equivalents per day for at least 2 weeks before the screening visit with no anticipated changes during the study.
5. A history of constipation due to opioid use for at least 1 month before the screening visit.
Constipation is defined as < 3 rescue-free (no laxative use during the prior 24 hours)
bowel movements (RFBMs) per week on average and 1 or more of the following:
i) Hard or lumpy stools.
ii) Straining during bowel movements.
iii) A sensation of incomplete evacuation after bowel movements.
6. All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 15 days after the last dose of test article administration. A subject is biologically capable of having children even if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives.
7. Willingness to discontinue all prestudy laxative therapy and use only the study-permitted rescue laxative during the screening, treatment, and follow-up periods.
8. Willingness and ability to participate in all aspects of the study, including use of
subcutaneous medication (administered by self or designee), completion of subject
evaluations, attending scheduled clinic visits, access to a telephone, and compliance with all protocol requirements as evidenced by written informed consent.
9. Ambulatory, capable of all self-care, and up and about more than 50% of waking hours.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Prior treatment with SC methylnaltrexone.
2. Pregnant or breastfeeding women.
3. A diagnosis of bowel obstruction, fecal incontinence, rectal prolapse, acute diverticulitis, or other significant GI disorders.
4. Any history of any inflammatory bowel disease or toxic megacolon or a history of
irritable bowel syndrome within 6 months before the screening visit.
5. A recent history of rectal bleeding unexplained by hemorrhoids or fissures.
6. Need for manual disimpaction or pelvic floor support techniques, including manual
maneuvers, within 14 days before the screening visit.
7. Clinical evidence of outlet obstruction or impaction. If suspected, a rectal examination must be performed to rule out obstruction or impaction.
8. A history of malignancy, other than basal- or squamous-cell skin carcinoma, within
5 years before the screening visit.
9. A history of laxative use due to chronic constipation before the initiation of opioid
therapy.
10. A history of alcohol or drug abuse within 1 year before the screening visit.
11. Any major illness/condition or unstable hepatic, renal, pulmonary, cardiovascular
(including uncontrolled hypertension), ophthalmologic, neurologic, psychiatric, or any
other medical condition that, in the investigator?s judgment, will substantially increase the risk associated with the subject?s participation in and completion of, the study, or could preclude the evaluation of the subject?s response.
12. A history or presence of symptomatic orthostatic hypotension.
13. Other clinically important abnormalities on screening physical examination findings, laboratory test results, or electrocardiogram (ECG) findings.
14. A calculated creatinine clearance (Cockcroft-Gault glomerular filtration rate [GFR])
< 30 mL/min.
15. Planned surgery during the study.
16. Known or suspected allergy to opioids, opioid derivatives, or opioid antagonists (eg, codeine, naltrexone, or naloxone) or other compounds related to these classes of medications.
17. Current treatment with partial opioid agonists (eg, buprenorphine) or combination agonists/antagonists.
18. Urine drug screen negative for the presence of opioids.
19. Urine drug screen positive for a substance of abuse that is not explained by a prescribed medication reported by the subject.
20. Patients who received opioid maintenance therapy (eg, methadone, buprenorphine) for the treatment of addiction.
21. Involvement in litigation related to the subject?s underlying medical condition.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Opioid-induced constipation in subjects with non-malignant pain Tratamiento del estreñimiento inducido por opiáceos en sujetos con dolor de origen no maligno
MedDRA version: 9.1 Level: LLT Classification code 10010774 Term: Constipation

Intervention(s)

Product Name: Methylnaltrexone bromide for SC injection: 12 mg (0.6 mL, 20 mg/mL) in prefilled syringes
Product Code: MOA-728
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methylnaltrexone Bromide
CAS Number: 73232-52-7
Current Sponsor code: 0151, MNTX/MOA
Other descriptive name: Naltrexone Methobromide, N-methylnaltrexone Bromide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Primary: To evaluate the safety, efficacy, and tolerability of subcutaneous MOA-728 versus placebo in subjects with nonmalignant pain who have opioid-induced constipation.

Secondary Objective: Secondary: To explore subject-reported outcomes for benefits of treatment with MOA-728.

Primary end point(s): Two coprimary efficacy endpoints are:
1. the proportion of subjects having a RFBM within 4 hours of the first dose administration, and
2. the percentage of injections resulting in any RFBM within 4 hours during the double-blind period.

Secondary ID(s)

3200K1-3357-WW