Assessment of Efficacy and Safety in Relieving Opioid-induced Constipation in Patients With Cancer-related Pain - Full Text View

Purpose

The purpose of this study is to compare the effect of NKTR-118 with placebo in the treatment of opioid-induced constipation (OIC) in patients with cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR).

The study consists of 2 parts; A initial 4-week treatment period (part A) and then a 12 week extension with active treatment (part B).

Condition	Intervention	Phase
Opioid-Induced Constipation	Drug: NKTR-118 Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Relieving Opioid-Induced Constipation (OIC) in Patients With Cancer-Related Pain

Resource links provided by NLM:

MedlinePlus related topics: Cancer Constipation

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Response to study drug, defined as having at least 3 Rescue-free bowel movements (RFBMs) per week during the 4-week treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. [ Time Frame: Will be collected daily through the 4-week treatment period. ] [ Designated as safety issue: No ]
Response (responder/non-responder) to study drug, where a responder is defined as having at least 3 Rescue-free bowel movements (RFBMs) per week during the 4-week treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks.

Secondary Outcome Measures:

Part A and Part B: Change from baseline in RFBMs/week [ Time Frame: Will be collected daily through the 4-week treatment period as well as the 12 week extension ] [ Designated as safety issue: No ]
Part A and Part B: mean number of days per week with at least 1 RFBM. [ Time Frame: Will be collected daily through the 4-week treatment period as well as athe 12 week extension ] [ Designated as safety issue: No ]
Part A: Time (in hours) to first post-dose RFBM [ Time Frame: Will be collected daily through the 4-week treatment period part A only. ] [ Designated as safety issue: No ]
Part A: Change from baseline in the degree of straining associated with RFBMs during the 4-week placebo-controlled treatment period. [ Time Frame: Will be collected daily through the 4-week treatment period part A only. ] [ Designated as safety issue: No ]
Part A: Change from baseline in stool consistency (BSS) during the 4-week placebo-controlled treatment period. [ Time Frame: Will be collected daily through the 4-week treatment period .part A only. ] [ Designated as safety issue: No ]
Part A: Percentage of days with complete evacuation during the 4-week placebo-controlled treatment period. [ Time Frame: Will be collected daily through the 4-week treatment period part A only. ] [ Designated as safety issue: No ]
Part A and B: Change from baseline in Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) total score and each domain score for Weeks 2 and 4. [ Time Frame: Part A: Will be evaluated at Visits 3, 5 and 6. Part B: will be evaluated at Visits 4 and 6. ] [ Designated as safety issue: No ]

Enrollment:	336
Study Start Date:	June 2011
Study Completion Date:	September 2012
Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 (part A and B) Oral treatment	Drug: NKTR-118 12.5 mg oral tablet once daily
Experimental: 2 (part A and B) Oral treatment	Drug: NKTR-118 25 mg oral tablet once daily
Placebo Comparator: 3 (part A only) Oral treatment	Drug: Placebo Oral treatment

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Provision of written informed consent prior to any study-specific procedures.
Men and women aged 18 or older.
Histologically or cytologically confirmed neoplasm causing pain and requiring management with opioids.
Self-reported active symptoms of OIC at screening (<3 RFBMs/week and experiencing >1 reported symptom of hard/lumpy stools, straining, or sensation of incomplete evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks); and Documented confirmed OIC (<3 RFBMs/week on average aver the 2-week OIC confirmation period.
Receiving a stable maintenance opioid regimen consisting of a total daily dose of >30 mg of oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies for a minimum of 4 weeks prior to screening for cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.

Exclusion Criteria:

Patients receiving Opioid regimen for treatment of pain other than related to cancer.
Any condition that may have affected the permeability of the blood-brain barrier, eg, known brain metastases, meningeal metastases, brain injury, multiple sclerosis, recent brain injury, uncontrolled epilepsy.
Patients with cancer-related pain due to ovarian cancer, leukaemia, or lymphoma are excluded. Patients with multiple myeloma will be allowed.
Patients requiring radiation therapy between the diaphragm and pelvis 4 weeks prior to Visit 1 (screening) and/or during Part A of the study are excluded. Any patients with suspected clinically relevant radiation-induced injury of small or large intestine are excluded.
Pregnancy or lactation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384292

Show 140 Study Locations

Sponsors and Collaborators

AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01384292 History of Changes
Other Study ID Numbers:	D3820C00006, 2011-001985-16
Study First Received:	June 28, 2011
Last Updated:	September 28, 2012
Health Authority:	United States: Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products Bulgaria: Bulgarian Drug Agency Czech Republic: State Institute for Drug Control Germany: Federal Institute for Drugs and Medical Devices Slovakia: State Institute for Drug Control South Africa: Medicine Control Council Spain: Spanish Agency of Medicines United Kingdom: Medicines and Healthcare Products Regulatory Agency Romania: National Medicines Agency (ANM) Poland: Ministry of Health and Social Welfare Croatia: Agency for Medicinal Product and Medical Devices

Keywords provided by AstraZeneca:

Cancer-Related Pain
Opioid-Induced Constipation
OIC

Additional relevant MeSH terms:

Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Analgesics, Opioid
Analgesics
Sensory System Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants

ClinicalTrials.gov processed this record on May 21, 2013