Healthy Subjects Clinical Trial
Official title:
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
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
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. |
Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
Country | Name | City | State |
---|---|---|---|
Germany | Research Site | Berlin |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
Germany,
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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