Colonic Motor Patterns in Healthy Volunteers

• Status: Completed
• Trial end date: 2019-05-09
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven
• Treatments: Codeine; Naloxegol

Criteria

Inclusion Criteria:

1. HV is a man or woman aged 18 to 65 years, inclusive, at prescreening.

2. 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.

3. HV has not used any opioid medication 14 days prior to randomization.

4. 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.

5. Female subjects must either be:

1. postmenopausal, defined as 52 years or older and amenorrheic for at least 2 years at prescreening,

2. surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),

3. abstinent, or

4. 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.

6. 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.

Exclusion Criteria:

1. 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.

2. HV has a history of diverticulitis.

3. 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).

4. HV has any of the following surgical history:

1. Any abdominal surgery within the 3 months prior to prescreening;

2. HV has a history of major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed).

5. HV has current evidence of laxative abuse.

6. 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.

7. HV has an unstable renal, hepatic, metabolic, or hematologic condition.

8. HV has a history of malignancy within 5 years before prescreening (except squamous and basal cell carcinomas and cervical carcinoma in situ).

9. 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.

10. 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).

11. 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.

12. HV is pregnant or breastfeeding.

13. 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.

14. No smoking on the day of the investigation and the day prior to it.

15. No consumption of grapefruit or grapefruit juice because it can increase Naloxegol plasma levels.