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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02446171
Other study ID # D3820C00035
Secondary ID
Status Completed
Phase Phase 1
First received April 29, 2015
Last updated July 28, 2015
Start date May 2015
Est. completion date July 2015

Study information

Verified date July 2015
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority Germany: Federal Institute for Drugs and Medical Devices (BfArM), Germany
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Completed
Enrollment 44
Est. completion date July 2015
Est. primary completion date July 2015
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 55 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science


Related Conditions & MeSH terms


Intervention

Drug:
Naloxegol 25 mg tablet, crushed, suspended in water, given orally
naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally
Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube
naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube
Naloxegol 25 mg (10 mL oral solution)
naloxegol 25 mg (10 mL oral solution)
Naloxegol 25 mg tablet, given orally
naloxegol 25 mg (1 tablet) whole tablet, given orally

Locations

Country Name City State
Germany Research Site Berlin

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Other Taste test assessment To assess the taste of the different formulations of Naloxegol. Within 1 hour after dosing (Treatments A and C only) No
Primary AUC0 - infinity AUC: Area under plasma concentration-time curve from time zero extrapolated to infinity pre-dose (0 hours [within 30 minutes prior to administration of the investigational medicinal product (IMP)]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Primary AUC(0-t) Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Primary Cmax Observed maximum plasma concentration pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary tmax Time to reach maximum plasma concentration pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary t½?z Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary MDT Mean dissolution time (whole tablet only) (calculated as MRTTreatment D [Reference] - MRTTreatment C [Test]) pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary MRT Mean residence time pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary ?z Terminal elimination rate constant pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary CL/F Apparent total body clearance after extravascular administration estimated as dose divided by AUC pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary Vz/F Apparent volume of distribution during the terminal phase after extravascular administration pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period No
Secondary Adverse events Standard AE collection. An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product For up to 9 weeks (starting with screening) Yes
Secondary Vital signs: blood pressure Systolic BP (SBP) (mmHg), Diastolic BP (DBP) (mmHg) At screening and for each treatment period on admission (Day -1), at pre-dose (0 hours) and post-dose at 24 and 48 hours, as well as at final follow-up (up to 9 weeks) Yes
Secondary Vital signs: pulse Pulse:
beats per minute [bpm]
At screening and for each treatment period on admission (Day -1), at pre-dose (0 hours) and post-dose at 24 and 48 hours, as well as at final follow-up (up to 9 weeks) Yes
Secondary physical examination general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, mouth and throat), lymph nodes, thyroid, musculoskeletal and neurological systems A full physical examination at screening and the final follow-up visit (maximum 9 weeks apart). Abbreviated physical examination on admission (on Day -1 of each treatment period) and at 48-hours post-dose to each treatment period (for up to 4 weeks) Yes
Secondary Columbia Suicide Severity Rating Scale (C-SSRS) To assess suicidal ideation and behavior C-SSRS will be performed at screening (version Baseline - Screening) and at the final follow-up visit (version Since Last Visit), (maximum 9 weeks apart) Yes
Secondary 12 lead ECG 12-lead ECG obtained after the subject rested in the supine position for at least 10 minutes At screening, first admission to the clinical unit (Visit 2, Day -1), 1.25 hours after each dose (Visits 2-5, Day 1), as well as at the final follow-up visit (up to 9 weeks); (total of 7 ECGs per subject who complete the study) Yes
Secondary safety laboratory assessments: Hematology Hematologic laboratory variables At screening and at the final follow-up visit (maximum 9 weeks apart); in addition, for the first and third treatment period at pre-dose Yes
Secondary safety laboratory assessments: clinical chemistry Serum clinical chemistry At screening and at the final follow-up visit (maximum 9 weeks apart); in addition, for the first and third treatment period at pre-dose Yes
Secondary safety laboratory assessments: urinalysis Urinalysis At screening and at the final follow-up visit (maximum 9 weeks apart); in addition, for the first and third treatment period at pre-dose Yes
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