N.a. pharmacokinetics of oxybutynin
Conditions
Interventions
Subject 1-8:
Multiple (7) doses of 2.5 mg oxybutynin, intravaginally administered via the
MedRing Alpha 2.0 in a concentration of 100 mg/ml for 48 hours (TID) (7 doses:
0h, 8h, 16h, 24h, 32h, 40h, 4
Sponsors
LiGalli BV
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Eligible subjects must meet all of the following inclusion criteria at screening: 1. Willing to give written informed consent and willing and able to comply with the study protocol. 2. Female subjects of child bearing potential (women of child bearing potential, WOCBP) aged between 18 and 45 years (inclusive). 3. Subject is in good general health, according to the investigator*s judgement based on vital signs, medical history, physical examination, and laboratory tests performed. 4. Body mass index between 18-32 kg*m2 (inclusive) and with a minimum body weight of 50 kg at screening. 5. Ability to communicate well with the investigator in the Dutch language and willing to comply with the study restrictions. 6. Using contraceptives of second generation containing ethinylestradiol and progesterone derivate. This includes a hormone-containing IUD (e.g. Mirena), second generation oral contraceptive pill, hormonal contraception using parenteral medroxyprogesteron or subcutaneous etonogestrel.
Exclusion criteria
Exclusion criteria: Eligible subjects must meet none of the following exclusion criteria at screening: 1. (A history of) any clinically significant medical condition or abnormalities, as judged by the investigator, in physical examination, laboratory test results (including chemistry panel with hepatic and renal panels, complete blood count, and urine dipstick) or electrocardiography (ECG) at screening. In the case of uncertain or questionable results, tests performed during screening may be repeated to confirm eligibility or judged by the investigator to be clinically irrelevant for healthy subjects. 2. Being a virgin. 3. History of sexual abuse/violence. 4. Last withdrawal bleeding within 24 hours before IMP administration. 5. Plan to discontinue oral contraceptive during study period. 6. Positive pregnancy test at screening or at baseline prior to IMP administration and/or lactating. 7. Having given birth vaginally or by caesarean section 6 months prior to screening. 8. Having had sexual intercourse or objects inserted vaginally that could potentially lacerate or damage the vaginal wall 24 hours prior to dosing. 9. Positive screening test for Hepatitis B/C and/or Human Immunodeficiency Virus (HIV) test at screening. 10. Positive screening PCR test for Chlamydia trachomatis or gonorrhea at screening. 11. Medical history of intra- and/or transvaginal operations that in the opinion of the investigator may interfere with placement or stability of the MedRing or absorption of the IMP. Exceptions may include endometrial curettage for e.g. miscarriage, abortion or LIS-excision of the cervix for CIN if performed > 3 months prior to screening. 12. Any known significant allergic reactions (urticaria or anaphylaxis) against oxybutynin, or multiple drug allergies (non-active hay fever is acceptable), or known hypersensitivity to components of the MedRing (polypropylene, styrene triblock copolymer, coloring agents, coating, glue). 13. Participation in any marketed or investigational drug or device study within 3 months or 5 half-lives (whichever is longer) prior to first dosing. 14. Use of any prescription medication and any other substance that in the opinion of the investigators may influence the outcome of the study within 21 days prior to study drug administrations, or less than five half-lives (whichever is longer, and during the course of the study). 15. Use of alcohol during the 24 hours prior to screening and/or an unwillingness to abstain from alcohol consumption during the stay at the clinical unit, and for at least 24 hours prior to each study visit. 16. Positive urine drug screen or alcohol test at screening and/or at study days. 17. Intake of grapefruit or grapefruit juice within 5 days of IMP administration, and/or unwillingness to abstain from the consumption of these products from 5 days prior to IMP administration until the last study visit. 18. Loss or donation of blood over 500 mL within four months prior to screening. 19. Any other condition that in the opinion of the investigator would complicate or compromise the study or the well-being of the subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Neurocart test battery: • Adaptive tracking (primary endpoint) o average performance (%); • Saccadic eye movements o saccadic reaction time (second), o saccadic peak velocity (degrees/second), and o saccadic inaccuracy (%); • Smooth pursuit eye movements o percentage of time the eyes of the subjects are in smooth pursuit of the target (%); • Pupillometry o left pupil/iris ratio o right pupil/iris ratio • Body sway o antero-posterior sway (mm); • Visual Analog Scales (VAS) according to Bond and Lader o mood (mm), o alertness (mm), and o calmness (mm). • N-Back task o average reaction time (ms) • Visual Verbal Learning Test (VVLT) memory testing o Immediate recall trial 3 (number correct), o Delayed recall (number correct), and o Delayed recognition (number correct) o Delayed recognition (reaction time correct) (msec) Other: • qEEG power spectra (resting eyes closed, eyes open condition) • Salivary flow • Visual near point acuity • Pulse rate (bpm) • Questionnaire assessing dry mouth | — |
Secondary
| Measure | Time frame |
|---|---|
| • Plasma concentrations of oxybutynin and desethyloxybutynin at predefined timepoints: AUCtau, CL/F, Cmax, Ctrough, t1/2, tmax, Vz/F • Local tolerability vaginal mucosa (inspection) • Tolerability questionnaires • Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit • Concomitant medication throughout the study at every study visit • Clinical laboratory tests (Hematology, blood chemistry and urinalysis) as per assessment schedule • Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)) as per assessment schedule • ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcF) as per assessment schedule • Vaginal pH measurement as per assessment schedule | — |
Countries
Netherlands
Outcome results
None listed