A Bioavailability Study With Alternate Methods of Administration of Naloxegol Tablets, and Solution

NCT ID: NCT02446171

Last Updated: 2017-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2015-07-31

Brief Summary

This clinical study is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of crushed naloxegol tablets, 25 mg and of a naloxegol solution formulation, 25 mg, compared to whole naloxegol tablets, 25 mg, in healthy subjects.

The main objective of this study is to determine the bioavailability of each of three alternative methods of naloxegol administration compared to whole naloxegol tablets given orally by assessment of the primary pharmacokinetic (PK) parameters of naloxegol

Detailed Description

This is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of naloxegol: crushed and suspended in water and administered orally (Treatment A),crushed and suspended in water administered via nasogastric tube (Treatment B), solution administered orally (Treatment C) and tablet swallowed as a whole (Treatment D).

Alternative ways of administering a tablet may be useful to help patients who, for different reasons, have difficulties with swallowing a whole tablet. Administration of dispersed (crushed) tablets suspended in water is a common way of administering drugs to these patients. A useful method in patients whose condition prevents swallowing is administration of dispersed tablets through nasogastric tubes. Additionally a solution formulation may be an attractive option for some patients including the pediatric population. The main aim in this clinical study is to investigate whether the blood concentrations of naloxegol (pharmacokinetic) after each treatment A, B and C is comparable to that after treatment D. Additionally, the safety and tolerability shall be assessed.

Conditions

Bioavailability; Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Treatments A-D-B-C sequence

Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4

Group Type: EXPERIMENTAL

Naloxegol 25 mg tablet, crushed, suspended in water, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally

Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube

Naloxegol 25 mg (10 mL oral solution)

Intervention Type: DRUG

naloxegol 25 mg (10 mL oral solution)

Naloxegol 25 mg tablet, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) whole tablet, given orally

Treatments B-A-C-D sequence

Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4

Group Type: EXPERIMENTAL

Naloxegol 25 mg tablet, crushed, suspended in water, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally

Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube

Naloxegol 25 mg (10 mL oral solution)

Intervention Type: DRUG

naloxegol 25 mg (10 mL oral solution)

Naloxegol 25 mg tablet, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) whole tablet, given orally

Treatments C-B-D-A sequence

Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4

Group Type: EXPERIMENTAL

Naloxegol 25 mg tablet, crushed, suspended in water, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally

Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube

Naloxegol 25 mg (10 mL oral solution)

Intervention Type: DRUG

naloxegol 25 mg (10 mL oral solution)

Naloxegol 25 mg tablet, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) whole tablet, given orally

Treatments D-C-A-B sequence

Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4

Group Type: EXPERIMENTAL

Naloxegol 25 mg tablet, crushed, suspended in water, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally

Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube

Naloxegol 25 mg (10 mL oral solution)

Intervention Type: DRUG

naloxegol 25 mg (10 mL oral solution)

Naloxegol 25 mg tablet, given orally

Intervention Type: DRUG

naloxegol 25 mg (1 tablet) whole tablet, given orally

Interventions

Naloxegol 25 mg tablet, crushed, suspended in water, given orally

naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally

Intervention Type: DRUG

Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube

naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube

Intervention Type: DRUG

Naloxegol 25 mg (10 mL oral solution)

naloxegol 25 mg (10 mL oral solution)

Intervention Type: DRUG

Naloxegol 25 mg tablet, given orally

naloxegol 25 mg (1 tablet) whole tablet, given orally

Intervention Type: DRUG

Other Intervention Names

Treatment A; (Test product); Treatment B; (Test product); Treatment C; (Test product); Treatment D; (Reference product)

Eligibility Criteria

Inclusion Criteria

• Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at screening and on admission to the clinical unit, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria:

• Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy; but not tubal ligation.
• Have a body mass index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Able to understand, read and speak the German language.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influence the results or the potential subject's ability to participate in the study.
• Current smokers or those who have smoked or used nicotine products within the previous 3 months.
• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.

Drugs include known CYP3A4 and/or P-gp inhibitors and inducers, e.g., diltiazem, verapamil, and erythromycin

• Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.

For females, hormonal replacement therapy is not allowed.

• Subject with a relevant history of a suicide attempt or suicidal behavior. Any recent suicidal ideation within the last 6 months (a level of 4 or 5), or who are at significant risk to commit suicide, as judged by the investigator using the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Applicable to subjects willing to participate in genetic research: Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainard Fuhr, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

PAREXEL International GmbH, Berlin

Locations

Research Site

Berlin, , Germany

Countries

Germany

References

Bui K, Birmingham B, Diva U, Berger B. An Open-Label, Randomized Bioavailability Study of Alternative Methods of Oral Administration of Naloxegol in Healthy Subjects. Clin Pharmacol Drug Dev. 2017 Jul;6(4):420-427. doi: 10.1002/cpdd.335. Epub 2017 Jan 27.

Reference Type: BACKGROUND

PMID: 28127938 (View on PubMed)

Other Identifiers

D3820C00035

Identifier Type: -

Identifier Source: org_study_id