Tolerability, Safety, and Feasibility of Naloxegol in Patients With Cancer and OIC (Opioid Induced Constipation)

NCT02839889 | Terminated Phase 4 Results

• 1 other identifier: D3820C00041
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine if naloxegol can be used in the treatment of opioid-induced constipation in patients with cancer and pain. This phase 4 study consists of a two week randomized double blind period followed by a two week open-label period.

Conditions

Cancer; Constipation; Pain

Outcome Measures

Primary Outcomes (9)

• Numerical Rating Scale (NRS) for Pain Change From Baseline

  Change from baseline in mean daily NRS (Numerical Rating Scale) values will be calculated as the post-baseline value minus the baseline. Baseline NRS is the mean daily NRS values recorded during the Opioid Induced Constipation (OIC) Confirmation period. Numeric Rating Scale is 0-10. 0 is no pain and 10 is worst possible pain. Lower values are a better outcome and higher values are a worse outcome. Post-baseline values were calculated as the mean of NRS scores during visits 2-4.

  Assessed from screening/Opioid Induced Constipation (OIC) Confirmation period through study completion, approximately 6 weeks.

• Daily Opioid Use Change From Baseline

  Change from baseline in mean daily opioid dose will be calculated as the post-baseline value minus the baseline value. Positive changes from baseline indicate there was a need to increase the opioid dose. Baseline daily opioid dose is the mean daily opioid dose recorded during the Opioid Induced Constipation (OIC) Confirmation period.

  Assessed from screening through study completion, approximately 6 weeks.

• Adverse Events Associated With Blood Laboratory Result Changes From Baseline

  Changes from Baseline to Visit 3 (approximately Day 15) for all patients will be calculated as the post-baseline test value minus the baseline test value.

  Change from Baseline at End of Double Blind Phase (Visit 3, approximately day 15)

• Electrocardiogram QTC Interval

  Changes from Baseline to Visit 3 (approximately Day 15) for Electrocardiogram (ECG) QTC interval data will be derived by subtracting the baseline value from the final assessment data.

  Change from Baseline at End of Double Blind Phase (Visit 3, approximately day 15)

• Electrocardiogram Heart Rate

  Changes from Baseline to Visit 3 (approximately Day 15) for Electrocardiogram (ECG) heart rate data will be derived by subtracting the baseline value from the final assessment data.

  Change from Baseline at End of Double Blind Phase (Visit 3, approximately day 15)

• Change From Baseline in Systolic Blood Pressure

  Change from Baseline in systolic blood pressure at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4.

  Change from Baseline in systolic blood pressure through study completion, approximately 6 weeks.

• Change From Baseline in Diastolic Blood Pressure

  Change from Baseline in diastolic blood pressure at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4.

  Change from Baseline in diastolic blood pressure through study completion, approximately 6 weeks.

• Change From Baseline in Respiratory Rate

  Change from Baseline in respiratory rate at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4.

  Change from Baseline in respiratory rate through study completion, approximately 6 weeks.

• Change From Baseline in Pulse Rate

  Change from Baseline in pulse rate at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4.

  Change from Baseline in pulse rate through study completion, approximately 6 weeks.

Secondary Outcomes (7)

• Rescue Free Bowel Movements (RFBM) Responder Rate

  Assessed from Baseline through Study Completion, approximately 6 weeks.

• Time to First Post-dose Rescue Free Laxation

  First dose date to first post-dose rescue free bowel movement

• Bristol Stool Scale (BSS) Score

  Assessed from baseline through Study Completion, approximately 6 weeks.

• Patient Assessment of Constipation Symptoms (PAC-SYM)

  day 1, day 15, day 29

• Patient Assessment of Constipation Quality of Life (PAC-QOL)

  day 1, day 15, day 29

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo once daily for two weeks

Drug: Placebo

Naloxegol

ACTIVE COMPARATOR

Naloxegol 25mg tablets once daily for two weeks

Drug: Naloxegol

Interventions

Naloxegol DRUG

Naloxegol 25mg tablets for two weeks, followed by a two week open-label period

Also known as: Movantik

Naloxegol

Placebo DRUG

Placebo once daily for two weeks, followed by two week open-label period

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18 or older: Women of child bearing potential must have a negative urine pregnancy test during the Screening/Opioid Induced Constipation (OIC) Confirmation/Baseline period, a history of no sexual activity or consistent use of an effective birth control method for at least 12 weeks prior to the study, and agreement that no sexual activity or the method of birth control will be continued during the study and for a period of 8 weeks after it ends; male patients who are sexually active must agree to use a barrier method of contraception (condom with spermicide) from the first dose of Investigational Product until 12 weeks after their last dose
• Able to follow instructions in English, give informed consent and to answer patient reported outcomes (PRO) questions by himself/herself; the patient will provide written informed consent before initiation of any study-related procedures
• Active cancer of any type with an investigator-estimated life expectancy ≥ 8 weeks and a Palliative Performance Status scale score ≥ 30%
• Patients receiving concurrent chemotherapy must have received and recovered from a minimum of 1 cycle of the current chemotherapy regimen upon consenting to the study and be considered stable in the opinion of the investigator
• Chronic cancer-related pain, defined as pain for a minimum of ≥2 weeks which on review by the investigator, can be attributed to the neoplasm or its treatment
• Daily treatment with an opioid drug which is taken at a dose equal to or greater than 20 mg morphine or its equivalent for at least one week, with no expectation of a decrease greater than 25% or an increase greater than 100% during the study period.
• Patients may or may not be on a stable laxative regimen, defined as daily use at a stable dose for \>7 days; if the patient is taking a stable dose, he or she must be willing to remain on that regimen for the 7 day confirmation period without titration or adjustments.
• History of constipation, defined through history and through participation in the Screening/OIC Confirmation/Baseline period:
• Patient history must include 2 or more of the following during defecations occurring in the two weeks prior to screening:
• \<3 spontaneous bowel movements per week
• hard/lumpy stools (Bristol Stool Scale Type 1 or 2) in more than 25% of defecations
• sensation of incomplete evacuation in more than 25% of defecations
• sensation of anorectal obstruction in more than 25% of defecations
• Straining during more than 25% of defecations
• Note: (spontaneous bowel movements (SBMs) are defined as not using a laxative if not already taking daily laxatives, or if taking daily laxatives, not using an additional laxative).

You may not qualify if:

• Cancer-related/medical comorbidity-related
• Patients with a past or current history of intra-abdominal neoplasm AND clinical findings that, on review by the investigator, may increase the risk of bowel perforation
• An active condition associated with clinically significant brain pathology, including known brain metastases, meningeal metastases, past traumatic brain injury, multiple sclerosis, uncontrolled epilepsy with signs or symptoms of compromised blood brain barrier
• Patients expected to undergo a first course of a chemotherapy regimen during the study period, patients who received a vinca alkaloid within 2 months, patients who have any history of vinca-associated GI autonomic neuropathy and/or constipation, or patients receiving a chemotherapy regimen including a VEGF-inhibitor (e.g., bevacizumab, sorafenib).
• Requiring radiation therapy between the diaphragm and pelvis 2 weeks prior to Visit 1 (screening) and/or during the study
• Any other significant and/or progressive condition (medical, neurological, psychiatric or metabolic) or symptom that could increase the risk of participation in the study or affect the interpretation of study data as determined by the investigator (e.g., uncontrolled hypothyroidism, inadequately controlled clinical depression, poorly controlled seizure disorder)
• Hemorrhagic diathesis
• Expected to have a surgical procedure requiring general anesthesia during the study period
• Other gastrointestinal disorders
• Medical conditions and treatments, which in the judgment of the investigator, may be associated with diarrhea, intermittent loose stools, or constipation, (e.g., active diverticular disease, peritonitis of any cause, inflammatory bowel disease, active irritable bowel syndrome, chronic idiopathic constipation).
• Any conditions that could affect the absorption or metabolism of the study drug (e.g., malabsorption syndrome, severe liver disease) as judged by the investigator
• Evidence of fecal impaction either by physical or x-ray exam
• Known or suspected mechanical GI obstruction
• Current peritoneal catheter for intra-peritoneal chemotherapy or dialysis
• Fecal ostomy

Sponsors & Collaborators

• Hospice of Henderson County, Inc.: lead
• AstraZeneca: collaborator

Study Sites (3)

MJHS Institute for Innovation in Palliative Care

New York, New York, 10006, United States

Location

Hospice of Henderson County, Inc

Flat Rock, North Carolina, 28731, United States

Location

Hospice of the Western Reserve, Inc.

Cleveland, Ohio, 44110, United States

Location

MeSH Terms

Conditions

Neoplasms; Constipation; Pain

Interventions

naloxegol

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations

Limitations and Caveats

Due to significant recruitment challenges enrollment was stopped. Only 5 patients were randomized (less than 12% of expected). There was insufficient data to perform the protocol specified analysis.

Results Point of Contact

• Title: Janet Bull, MD
• Organization: Four Seasons Compassion for Life

jbull@fourseasonscfl.org

8286926178

Study Officials

• Janet Bull, MD

  Hospice of Henderson County, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Medical Officer

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: July 21, 2016
• Study Start: September 1, 2016
• Primary Completion: January 11, 2018
• Study Completion: January 11, 2018
• Last Updated: March 5, 2019
• Results First Posted: March 5, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)