Colonic Motor Patterns in Healthy Volunteers

NCT05770960 | Completed Phase 4

• 1 other identifier: S61159
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Characterization of motor patterns with opioid agonists (codeine) ingestion, and their reversal by a peripherally acting mu-opioid receptor antagonist (Naloxegol).

Conditions

Opioid-Induced Constipation

Keywords

Naloxegol; Codeine; Colonic manometry; HRM; Motility; Opioid induced constipation; OIC

Outcome Measures

Primary Outcomes (1)

• Overall prevalence of anterograde colonic motor patterns in the different treatment categories.

  Observational

  3 times for 6 hours

Secondary Outcomes (4)

• Evaluation of the overall prevalence of the other colonic motor patterns (retrograde propagating sequences, simultaneous pressure waves, cyclic propagating sequences, high-amplitude propagating sequences)

  3 times for 6 hours

• Evaluation of the overall prevalence of high-amplitude propagating sequences after Bisacodyl

  3 times for 6 hours

• Evaluation of the colonic motility index in the left, right and sigmoid colon.

  3 times for 6 hours

• Percentage of Participants reporting Adverse Events (AE).

  3 times for 6 hours

Study Arms (3)

Naloxegol - Codeine phosphate

ACTIVE COMPARATOR

Participants will receive Naloxegol 25 mg and Codeine syrup in 30 mL and an additional 15 mL at a later stage during the day.

Drug: Naloxegol; Drug: codeine phosphate

Placebo - Codeine phosphate

OTHER

Participants will receive Placebo instaid of Naloxegol 25 mg and Codeine syrup in 30 mL and an additional 15 mL at a later stage during the day.

Drug: codeine phosphate; Other: Placebo

Naloxegol - Placebo

OTHER

Participants will receive Naloxegol 25 mg and Sirupus simplex syrup (as a placebo alternative for Codeine syrup) in 30 mL and an additional 15 mL at a later stage during the day.

Drug: Naloxegol; Other: Placebo

Interventions

Naloxegol DRUG

Oral administration of Naloxegol after waking up from the Midazolam administration during the colonoscopy.

Also known as: Movantik, Moventig

Naloxegol - Codeine phosphate; Naloxegol - Placebo

codeine phosphate DRUG

Oral administration of Codeine after waking up from the Midazolam administration during the colonoscopy.

Also known as: Bronchodine

Naloxegol - Codeine phosphate; Placebo - Codeine phosphate

Placebo OTHER

Oral administration of siripus simplex syrup after waking up from the Midazolam administration during the colonoscopy.

Also known as: Siripus simplex syrup

Naloxegol - Placebo; Placebo - Codeine phosphate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HV is a man or woman aged 18 to 65 years, inclusive, at prescreening.
• Normal stool pattern of between 3 defecations per day and 3 per week with a Bristol Stool Form Scale (BSFS) of 1, 2, 6 or 7 in less than 25% of defaecations.
• HV has not used any opioid medication 14 days prior to randomization.
• Medications taken for the treatment of allergies, chronic medical conditions, and migraine headaches can be taken during this study (with the exception of opioids for acute treatment of migraines). HV must be on a stable dose of medication for chronic migraines or preventative therapy for at least 1 month at prescreening. HV on stable doses of antidepressants (i.e., for the 3 months prior to prescreening) will be allowed to participate in the study. As needed use of benzodiazepines, if habitual, is permitted.
• Female subjects must either be:
• postmenopausal, defined as 52 years or older and amenorrheic for at least 2 years at prescreening,
• surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
• abstinent, or
• if sexually active, be practicing an effective method of birth control such as hormonal prescription oral contraceptives, progesterone implants or injections, contraceptive patch, intrauterine device, or male partner with a vasectomy.
• HV must sign an informed consent document before the initiation of any study-related procedures indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.

You may not qualify if:

• HV has a history of inflammatory or immune-mediated GI disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis), celiac disease and functional bowel disorder.
• HV has a history of diverticulitis.
• HV has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (eg, aortoiliac disease).
• HV has any of the following surgical history:
• Any abdominal surgery within the 3 months prior to prescreening;
• HV has a history of major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed).
• HV has current evidence of laxative abuse.
• HV has a history of a cardiovascular event, including stroke, myocardial infarction, congestive heart failure, or transient ischemic attack within 6 months prior to prescreening.
• HV has an unstable renal, hepatic, metabolic, or hematologic condition.
• HV has a history of malignancy within 5 years before prescreening (except squamous and basal cell carcinomas and cervical carcinoma in situ).
• HV has abnormal thyroid function test as confirmed by thyroid-stimulating hormone \<0.3 mcIU/mL or ≥5 mcIU/mL at Prescreening. However, patients who are clinically euthyroid due to thyroid supplement are candidates for the study.
• HV has current (within 14 days of randomization) or expected use of any narcotic or opioid containing agents, docusate, enemas, GI preparations (including antacids containing aluminum or magnesium, antidiarrheal agents, antinausea agents, antispasmodic agents, bismuth, or prokinetic agents).
• HV has received an investigational drug or used an investigational medical device within 30 days prior to randomization, or is currently enrolled in an investigational study.
• HV is pregnant or breastfeeding.
• HV has any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the HV from meeting or performing study requirements.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Opioid-Induced Constipation

Interventions

naloxegol; Codeine

Condition Hierarchy (Ancestors)

Constipation; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Jan Tack, Professor

  UZ Leuven / KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double-blind cross-over design (three-way)

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: March 16, 2023
• Study Start: June 27, 2018
• Primary Completion: May 9, 2019
• Study Completion: May 9, 2019
• Last Updated: March 16, 2023

Record last verified: 2023-03

Locations

BE (1)