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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Bioavailability

Treatments: Drug: Naloxegol 25 mg (10 mL oral solution); Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube; Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally; Drug: Naloxegol 25 mg tablet, given orally

Study type: Interventional

Funder types: Industry

Identifiers

NCT02446171

D3820C00035

Details and patient eligibility

About

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

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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44 participants in 4 patient groups

Treatments A-D-B-C sequence

Experimental group

Description:

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

Treatment:

Drug: Naloxegol 25 mg tablet, given orally

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

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

Drug: Naloxegol 25 mg (10 mL oral solution)

Treatments B-A-C-D sequence

Experimental group

Description:

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

Treatment:

Drug: Naloxegol 25 mg tablet, given orally

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

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

Drug: Naloxegol 25 mg (10 mL oral solution)

Treatments C-B-D-A sequence

Experimental group

Description:

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

Treatment:

Drug: Naloxegol 25 mg tablet, given orally

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

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

Drug: Naloxegol 25 mg (10 mL oral solution)

Treatments D-C-A-B sequence

Experimental group

Description:

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

Treatment:

Drug: Naloxegol 25 mg tablet, given orally

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

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

Drug: Naloxegol 25 mg (10 mL oral solution)