Trial Outcomes & Findings for Bioequivalence of Two Transdermal Clonidine Administrations in Healthy Volunteers (NCT NCT02096744)
NCT ID: NCT02096744
Last Updated: 2015-07-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
56 participants
Primary outcome timeframe
1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h after patch administration
Results posted on
2015-07-16
Participant Flow
This study was conducted in three separate groups.
Participant milestones
| Measure |
Catapres®-TTS-3 Crossover 1: TTS-3 Oppanol Then TTS-3 Vistanex
Catapres®-TTS(Transdermal Therapeutic System)-3 (0.3 mg/24 hr) Oppanol® (T1) first, followed by Catapres®-TTS-3 (0.3 mg/24 hr) Vistanex™ (R1). Followed by simultaneous administration of TTS-1 Oppanol® (T2) and TTS-1 Vistanex™ (R2) patches each delivering 0.1mg clinidine/24h.
|
Catapres®-TTS-3 Crossover 2: TTS-3 Vistanex Then TTS-3 Oppanol
Catapres®-TTS-3 (0.3 mg/24 hr) Vistanex™ (R1) first, followed by Catapres®-TTS-3 (0.3 mg/24 hr) Oppanol® (T1). Followed by simultaneous administration of TTS-1 Oppanol® (T2) and TTS-1 Vistanex™ (R2) patches each delivering 0.1mg clinidine/24h.
|
|---|---|---|
|
Treatment Period 1(7 Days)
STARTED
|
29
|
29
|
|
Treatment Period 1(7 Days)
COMPLETED
|
28
|
28
|
|
Treatment Period 1(7 Days)
NOT COMPLETED
|
1
|
1
|
|
Washout Period 1(7 Days)
STARTED
|
28
|
28
|
|
Washout Period 1(7 Days)
COMPLETED
|
28
|
28
|
|
Washout Period 1(7 Days)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2 (7 Days)
STARTED
|
28
|
28
|
|
Treatment Period 2 (7 Days)
COMPLETED
|
28
|
28
|
|
Treatment Period 2 (7 Days)
NOT COMPLETED
|
0
|
0
|
|
Washout Period 2 (3 Days)
STARTED
|
28
|
28
|
|
Washout Period 2 (3 Days)
COMPLETED
|
28
|
28
|
|
Washout Period 2 (3 Days)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 3 (7 Days)
STARTED
|
28
|
28
|
|
Treatment Period 3 (7 Days)
COMPLETED
|
28
|
27
|
|
Treatment Period 3 (7 Days)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Catapres®-TTS-3 Crossover 1: TTS-3 Oppanol Then TTS-3 Vistanex
Catapres®-TTS(Transdermal Therapeutic System)-3 (0.3 mg/24 hr) Oppanol® (T1) first, followed by Catapres®-TTS-3 (0.3 mg/24 hr) Vistanex™ (R1). Followed by simultaneous administration of TTS-1 Oppanol® (T2) and TTS-1 Vistanex™ (R2) patches each delivering 0.1mg clinidine/24h.
|
Catapres®-TTS-3 Crossover 2: TTS-3 Vistanex Then TTS-3 Oppanol
Catapres®-TTS-3 (0.3 mg/24 hr) Vistanex™ (R1) first, followed by Catapres®-TTS-3 (0.3 mg/24 hr) Oppanol® (T1). Followed by simultaneous administration of TTS-1 Oppanol® (T2) and TTS-1 Vistanex™ (R2) patches each delivering 0.1mg clinidine/24h.
|
|---|---|---|
|
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
Bioequivalence of Two Transdermal Clonidine Administrations in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Overall Study
n=58 Participants
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).
|
|---|---|
|
Age, Continuous
|
41.3 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h after patch administrationPopulation: 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.
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.
Outcome measures
| Measure |
Catapres®-TTS-3 With Oppanol®
n=52 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Oppanol® (T1)
|
Catapres®-TTS-3 With Vistanex™
n=50 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Vistanex™ (R1)
|
|---|---|---|
|
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 19.0
|
80641.47 pg*h/mL
Geometric Coefficient of Variation 19.0
|
PRIMARY outcome
Timeframe: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administrationPopulation: 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.
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.
Outcome measures
| Measure |
Catapres®-TTS-3 With Oppanol®
n=52 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Oppanol® (T1)
|
Catapres®-TTS-3 With Vistanex™
n=50 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Vistanex™ (R1)
|
|---|---|---|
|
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
|
668.893 pg/mL
Geometric Coefficient of Variation 16.6
|
SECONDARY outcome
Timeframe: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administrationPopulation: 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.
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.
Outcome measures
| Measure |
Catapres®-TTS-3 With Oppanol®
n=52 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Oppanol® (T1)
|
Catapres®-TTS-3 With Vistanex™
n=50 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Vistanex™ (R1)
|
|---|---|---|
|
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
|
115903.34 pg*h/mL
Geometric Coefficient of Variation 15.8
|
SECONDARY outcome
Timeframe: 1 hour (h) before patch administration and 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h after patch administrationPopulation: 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.
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.
Outcome measures
| Measure |
Catapres®-TTS-3 With Oppanol®
n=52 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Oppanol® (T1)
|
Catapres®-TTS-3 With Vistanex™
n=50 Participants
Subject to receive 0.3 mg/24 hr Catapres®-TTS-3 Vistanex™ (R1)
|
|---|---|---|
|
Cmax (Maximum Concentration of Clonidine in Plasma)
|
813.516 pg/mL
Geometric Coefficient of Variation 16.7
|
781.896 pg/mL
Geometric Coefficient of Variation 16.7
|
Adverse Events
TTS-3: Oppanol® (T1)
Serious events: 0 serious events
Other events: 46 other events
Deaths: 0 deaths
TTS-3: Vistanex™ (R1)
Serious events: 0 serious events
Other events: 45 other events
Deaths: 0 deaths
TTS-1: Vistanex™ (R2) + Oppanol® (T2)
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
TTS-3: Oppanol® (T1)
n=57 participants at risk
Administration of TTS-3 with Oppanol®
|
TTS-3: Vistanex™ (R1)
n=57 participants at risk
Administration of TTS-3 with Vistanex™
|
TTS-1: Vistanex™ (R2) + Oppanol® (T2)
n=56 participants at risk
Simultaneous administration of TTS-1 with Oppanol® and TTS-1 with Vistanex™
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
3/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Gastrointestinal disorders
Dry mouth
|
10.5%
6/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
7.0%
4/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Gastrointestinal disorders
Infrequent bowel movements
|
10.5%
6/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
14.0%
8/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Gastrointestinal disorders
Nausea
|
5.3%
3/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
1.8%
1/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
1.8%
1/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
General disorders
Application site erythema
|
40.4%
23/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
33.3%
19/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
17.9%
10/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
General disorders
Application site papules
|
21.1%
12/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
14.0%
8/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
10.7%
6/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
General disorders
Application site pruritus
|
8.8%
5/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
7.0%
4/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
General disorders
Fatigue
|
5.3%
3/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
5.3%
3/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Nervous system disorders
Dizziness
|
7.0%
4/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
10.5%
6/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
5.4%
3/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Nervous system disorders
Headache
|
14.0%
8/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
12.3%
7/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
5.4%
3/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Psychiatric disorders
Insomnia
|
3.5%
2/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
7.0%
4/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
|
Vascular disorders
Orthostatic hypotension
|
19.3%
11/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
5.3%
3/57 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
0.00%
0/56 • From patch administration until at most 7 days after patch removal, i.e., up to 14 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER