Phase 1
Completed N=44
A Bioavailability Study With Alternate Methods of Administration of Naloxegol Tablets, and Solution
Bioavailability · Healthy Subjects
Source: ClinicalTrials.gov NCT02446171 ↗
Enrolled (actual)
44
Serious AEs
0.0%
Results posted
Jun 2016
Primary outcomePrimary: Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity). — 191; 192; 179; 191 h*ng/mL
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity). |
191; 192; 179; 191 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC 0-t). |
188; 190; 178; 188 | — |
| PRIMARY Observed Maximum Plasma Concentration (Cmax). |
39.2; 40.1; 40.2; 39.7 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax). |
0.75; 1.50; 0.50; 1.00 | — |
| SECONDARY Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz). |
9.92; 8.78; 9.28; 9.22 | — |
| SECONDARY Mean Dissolution Time (MDT). |
1.29 | — |
| SECONDARY Mean Residence Time (MRT). |
6.94; 6.54; 6.21; 6.72 | — |
| SECONDARY Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F). |
131; 130; 140; 131 | — |
| SECONDARY Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F). |
1738; 1513; 1731; 1640 | — |
| SECONDARY Percentage of Participants With Adverse Events (AE). |
9.5; 7.0; 11.6; 18.6 | — |
| SECONDARY Mean Change From Baseline for Vital Signs of Supine Systolic and Diastolic Blood Pressure. |
-2; -4; -1; 0; 4; -2 | — |
| SECONDARY Mean Change From Baseline for Vital Signs in Supine Pulse Rate. |
1; 0; 1; 2; 5; 4 | — |
| SECONDARY Participants With Significant Findings in Physical Examination. |
0; 0; 0; 0 | — |
| SECONDARY Participants With Significant Findings in Columbia-Suicide Severity Rating Scale (C-SSRS). |
0; 0; 0; 0 | — |
| SECONDARY Participants With Significant Findings in 12-Lead Electrocardiography (ECG). |
0; 0; 0; 0 | — |
| SECONDARY Participants With Significant Findings in Hematology, Clinical Chemistry and Urinalysis. |
0; 0; 0; 0 | — |
| SECONDARY Taste Test Assessment. |
0.0; 7.0; 0.0; 0.0; 0.0; 0.0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02446171). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.