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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01309841




Registration number
NCT01309841
Ethics application status
Date submitted
4/03/2011
Date registered
7/03/2011
Date last updated
1/06/2015

Titles & IDs
Public title
Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Patients With Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC)
Secondary ID [1] 0 0
2011-001987-24
Secondary ID [2] 0 0
D3820C00004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid-Induced Constipation (OIC) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Mental Health 0 0 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NKTR-118
Treatment: Drugs - NKTR-118
Treatment: Drugs - Placebo

Experimental: 1 - Oral treatment

Experimental: 2 - Oral treatment

Placebo comparator: 3 - Oral treatment


Treatment: Drugs: NKTR-118
12.5 mg oral tablet once daily

Treatment: Drugs: NKTR-118
25 mg oral tablet once daily

Treatment: Drugs: Placebo
Oral tablet once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
Timepoint [1] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [1] 0 0
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
Timepoint [1] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [2] 0 0
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Change From Baseline in Degree of Straining
Timepoint [4] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [5] 0 0
Change From Baseline in Stool Consistency (Bristol Stool Scale)
Timepoint [5] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [6] 0 0
Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
Timepoint [6] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [7] 0 0
Change From Baseline in Mean Spontaneous Bowel Movements/Week
Timepoint [7] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [8] 0 0
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup
Timepoint [8] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [9] 0 0
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
Timepoint [9] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [10] 0 0
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
Timepoint [10] 0 0
Baseline (Week 1) to end of treatment (Week 12)

Eligibility
Key inclusion criteria
* Provision of written informed consent prior to any study-specific procedures.
* Men and women who are between the ages of =18 and <85 years.
* Self-reported active symptoms of OIC at screening (<3 SBMs/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 SBMs/week on average over the 2-week OIC confirmation period.
* Receiving a stable maintenance opioid regimen consisting of a total daily dose of 30 mg to 1000 mg of oral morphine, or equianalgesic amount(s) of 1 or more other opioid therapies for a minimum of 4 weeks prior to screening for non-cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.
* Willingness to stop all laxatives and other bowel regimens including prune juice and herbal products throughout the 2-week OIC confirmation period and the 12-week treatment period, and to use only bisacodyl as rescue medication if a BM has not occurred within at least 72 hours of the last recorded BM.
Minimum age
18 Years
Maximum age
84 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients receiving Opioid regimen for treatment of pain related to cancer.
* History of cancer within 5 years from first study visit with the exception of basal cell cancer and squamous cell skin cancer.
* Medical conditions and treatments associated with diarrhea, intermittent loose stools, or constipation.
* Other issues to the gastrointestinal tract that could impose a risk to the patient.
* Pregnancy or lactation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2012
Sample size
Target
Accrual to date
Final
652
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Research Site - Broadmeadow
Recruitment hospital [2] 0 0
Research Site - Darlinghurst
Recruitment hospital [3] 0 0
Research Site - Port Kembla
Recruitment hospital [4] 0 0
Research Site - Westmead
Recruitment hospital [5] 0 0
Research Site - Greenslopes
Recruitment hospital [6] 0 0
Research Site - Adelaide
Recruitment hospital [7] 0 0
Research Site - Fremantle
Recruitment hospital [8] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
- Broadmeadow
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Port Kembla
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment postcode(s) [5] 0 0
- Greenslopes
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Fremantle
Recruitment postcode(s) [8] 0 0
- Nedlands
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Florida
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Georgia
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Idaho
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Illinois
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Indiana
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Iowa
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Maryland
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Massachusetts
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Michigan
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Mississippi
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Missouri
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Montana
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Nebraska
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Nevada
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
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Texas
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Utah
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Washington
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Germany
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BE
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Germany
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BR
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Germany
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HE
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Germany
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HH
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MV
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Germany
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NI
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Germany
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NW
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Germany
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RP
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Germany
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SH
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Germany
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SN
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Slovakia
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Banska Bystrica
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Slovakia
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Bratislava
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Slovakia
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Kosice
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Slovakia
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Presov

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the effect and safety of NKTR-118 treatment of opioid-induced constipation in patients with non-cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR).
Trial website
https://clinicaltrials.gov/study/NCT01309841
Trial related presentations / publications
Webster L, Tummala R, Diva U, Lappalainen J. A 12-week extension study to assess the safety and tolerability of naloxegol in patients with noncancer pain and opioid-induced constipation. J Opioid Manag. 2016 Nov/Dec;12(6):405-419. doi: 10.5055/jom.2016.0360.
Lawson R, King F, Marsh K, Altincatal A, Cimen A. Impact of Treatment with Naloxegol for Opioid-Induced Constipation on Patients' Health State Utility. Adv Ther. 2016 Aug;33(8):1331-46. doi: 10.1007/s12325-016-0365-y. Epub 2016 Jun 24.
Tack J, Lappalainen J, Diva U, Tummala R, Sostek M. Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United European Gastroenterol J. 2015 Oct;3(5):471-80. doi: 10.1177/2050640615604543.
Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014 Jun 19;370(25):2387-96. doi: 10.1056/NEJMoa1310246. Epub 2014 Jun 4.
Public notes

Contacts
Principal investigator
Name 0 0
Mark Sostek
Address 0 0
AstraZeneca Pharmaceuticals, Wilm DE
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01309841