Healthy
Conditions
Brief summary
To establish the bioequivalence and adhesion properties of transdermal clonidine prepared with Oppanol® brands of polyisobutylene (PIB) vs. transdermal clonidine prepared with VistanexTM brands of polyisobutylene (PIB) in healthy male and female volunteers.
Interventions
DRUGCatapres-TTS-1
Catapres-TTS-1 Oppanol
DRUGIntervention 1: Catapres-TTS-3
Catapres-TTS-3 Oppanol
DRUGIntervention 2: Catapres-TTS-3
Catapres-TTS-3 Vistanex
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. A complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests 2. Age greater than or equal to 18 and Age less than or equal to 65 years 3. BMI greater than or equal to 18.5 and BMI less than or equal to 32.0 kg/m2 (Body Mass Index) 4. Signed and dated written informed consent prior to admission to the study 5. Male subjects, or females who meet any of the following criteria from at least 30 days before the first study drug administration and until 30 days after trial completion: * Using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD) * Sexually abstinent * Have a vasectomised sexual partner (vasectomy at least one year prior to enrolment) * Surgically sterilised (including hysterectomy) * Postmenopausal defined as at least one year of spontaneous amenorrhea
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal 2. Repeated measurement of supine systolic blood pressure outside the range of 100-140 mm Hg or diastolic blood pressure outside the range of 60-90 mm Hg or pulse less than 55 bpm 3. Any subject with orthostatic hypotension at baseline screening exam 4. Any laboratory value outside the reference range 5. Any evidence of a clinically relevant concomitant disease 6. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic (including insulin-dependent diabetes), immunological or hormonal disorders 7. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders (such as depression) or neurological disorders (such as neuropathy) 8. History of relevant orthostatic hypotension, fainting spells or blackouts 9. Chronic or relevant acute infections 10. History of relevant allergy/hypersensitivity 11. Intake of drugs with a long half-life (greater than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial. 12. Use of drugs which might reasonably influence the results of the trial within 10 days prior to administration or during the trial 13. Participation in another trial with an investigational drug within two months prior to administration or during the trial 14. Any concomitant therapy 15. Smoker 16. History of alcohol abuse 17. History of drug abuse 18. Blood donation 19. Excessive physical activities (within one week prior to administration or during the trial) 20. Subjects should not swim during the treatment periods of the trial 21. Any condition of the skin, including eczema, psoriasis, or lymphedema, that involves the upper arm in the area that would be utilized for application of the treatments 22. Pregnancy or planning to become pregnant within two months of study completion 23. Positive pregnancy test 24. A screening ECG that displays first-degree atrioventricular block (P-R interval \> 0.20 seconds) or other conduction disturbance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-168 (Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to 168 h) | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h after patch administration | AUC0-168 (area under the concentration-time curve of clonidine in plasma over the time interval from 0 to 168 h) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. |
| Cavg (Average of Measured Concentrations of Clonidine in Plasma on Days 5, 6, and 7) | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration | Cavg (average of measured concentrations of clonidine in plasma on Days 5, 6, and 7) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-inf(Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to Infinity) | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration | AUC 0-inf(area under the concentration-time curve of clonidine in plasma over the time interval from 0 to infinity) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. |
| Cmax (Maximum Concentration of Clonidine in Plasma) | 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration | Cmax (maximum concentration of clonidine in plasma) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. |
Countries
United States
Participant flow
Recruitment details
This study was conducted in three separate groups.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study A randomised, double-blind, 2-way crossover design, followed by a period for assessment of adhesive properties of the clonidine patch.
In the crossover part of the trial, subjects were treated with either Catapres®-TTS delivering 0.3 mg clonidine/24 h (TTS-3) in the Oppanol® formulation (test treatment T1) or Catapres®-TTS-3 (0.3 mg/24 h) with Vistanex™ formulation (reference treatment R1) in each period. In the adhesion phase of the trial, subjects were treated simultaneously with Oppanol® (test treatment T2) and Vistanex™ (reference treatment R2) patches, each delivering 0.1 mg clonidine/24 h (TTS-1). | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1(7 Days) | Accidental early removal of the patch | 0 | 1 |
| Treatment Period 1(7 Days) | Non compliance with the site rule | 1 | 0 |
| Treatment Period 3 (7 Days) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 57 | 45 / 57 | 23 / 56 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 | 0 / 56 |
Outcome results
Primary
AUC0-168 (Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to 168 h)
AUC0-168 (area under the concentration-time curve of clonidine in plasma over the time interval from 0 to 168 h) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Time frame: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h after patch administration
Population: PKS included all treated subjects who provided at least one observation for at least one primary endpoint without protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Catapres®-TTS-3 With Oppanol® | AUC0-168 (Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to 168 h) | 82517.99 pg*h/mL | Geometric Coefficient of Variation 19 |
| Catapres®-TTS-3 With Vistanex™ | AUC0-168 (Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to 168 h) | 80641.47 pg*h/mL | Geometric Coefficient of Variation 19 |
p-value: <0.000190% CI: [95.74, 109.37]ANOVA
Primary
Cavg (Average of Measured Concentrations of Clonidine in Plasma on Days 5, 6, and 7)
Cavg (average of measured concentrations of clonidine in plasma on Days 5, 6, and 7) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Time frame: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration
Population: PKS included all treated subjects who provided at least one observation for at least one primary endpoint without protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Catapres®-TTS-3 With Oppanol® | Cavg (Average of Measured Concentrations of Clonidine in Plasma on Days 5, 6, and 7) | 697.327 pg/mL | Geometric Coefficient of Variation 16.6 |
| Catapres®-TTS-3 With Vistanex™ | Cavg (Average of Measured Concentrations of Clonidine in Plasma on Days 5, 6, and 7) | 668.893 pg/mL | Geometric Coefficient of Variation 16.6 |
p-value: <0.000190% CI: [98.367, 110.487]ANOVA
Secondary
AUC0-inf(Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to Infinity)
AUC 0-inf(area under the concentration-time curve of clonidine in plasma over the time interval from 0 to infinity) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Time frame: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration
Population: PKS included all treated subjects who provided at least one observation for at least one primary endpoint without protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Catapres®-TTS-3 With Oppanol® | AUC0-inf(Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to Infinity) | 119127.55 pg*h/mL | Geometric Coefficient of Variation 15.8 |
| Catapres®-TTS-3 With Vistanex™ | AUC0-inf(Area Under the Concentration-time Curve of Clonidine in Plasma Over the Time Interval From 0 to Infinity) | 115903.34 pg*h/mL | Geometric Coefficient of Variation 15.8 |
p-value: <0.000190% CI: [97.25, 108.63]ANOVA
Secondary
Cmax (Maximum Concentration of Clonidine in Plasma)
Cmax (maximum concentration of clonidine in plasma) The values for geometric mean and gCV are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Time frame: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administration
Population: PKS included all treated subjects who provided at least one observation for at least one primary endpoint without protocol violations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Catapres®-TTS-3 With Oppanol® | Cmax (Maximum Concentration of Clonidine in Plasma) | 813.516 pg/mL | Geometric Coefficient of Variation 16.7 |
| Catapres®-TTS-3 With Vistanex™ | Cmax (Maximum Concentration of Clonidine in Plasma) | 781.896 pg/mL | Geometric Coefficient of Variation 16.7 |
p-value: <0.000190% CI: [98.148, 110.294]ANOVA