Clinical Trial Results:
A Phase 1 Open-Label Study of the Pharmacokinetics of Tacrolimus Cream B 0.1% after Twice Daily Topical Administration in Adolescents (more than or equal to 12 to less than or equal to 17 years of age) with Psoriasis
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Summary
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EudraCT number |
2006-002738-39 |
Trial protocol |
LV |
Global end of trial date |
03 May 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2016
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First version publication date |
13 Jun 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
04-7-011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Astellas Pharma US, Inc.
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Sponsor organisation address |
1 Astellas Way, Northbrook, IL, United States, 60062
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Public contact |
Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., Astellas.resultsdisclosure@astellas.com
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Scientific contact |
Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., Astellas.resultsdisclosure@astellas.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 May 2007
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 May 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
03 May 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to determine the pharmacokinetics and safety of tacrolimus cream 0.1% in adolescents (≥ 12 to ≤ 17 years of age) with plaque psoriasis affecting ≥ 10% body surface area (BSA) (excluding the scalp) who were treated topically for 29 days (4 weeks).
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Protection of trial subjects |
This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki.
Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Dec 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Latvia: 12
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Country: Number of subjects enrolled |
Bulgaria: 10
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Worldwide total number of subjects |
22
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EEA total number of subjects |
22
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
22
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
Participants aged 12 to 17 years with a diagnosis of plaque psoriasis affecting ≥ 10% BSA and a Physician’s Static Global Assessment (PSGA) ≥ 3 were enrolled. | ||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Tacrolimus cream 0.1% | ||||||||||
Arm description |
- | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Tacrolimus cream 0.1%
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Investigational medicinal product code |
FK506
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Other name |
Tacrolimus cream B-0.1%
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Pharmaceutical forms |
Cream
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Routes of administration |
Topical use
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Dosage and administration details |
The investigator defined the areas for treatment at baseline (day 1) and each study visit. Tacrolimus cream 0.1% was applied topically as a thin coating on the specified treatment area twice daily for 28 days and once in the morning of day 29 (end of treatment/EOT). Applications were to occur at consistent times, approximately 12 hours apart. Participants were to wait at least 2 hours after application of study drug before bathing, showering, or heavy exercise. Any new non-scalp plaque lesions appearing after day 1 or existing plaques that increased in size were to be treated by the participant until clear plus an additional 7 days or until day 29, whichever came first. If the affected area decreased in size, the participant was to continue treatment of the area until day 29 or until the area was clear plus an additional 7 days, whichever came first.
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Baseline characteristics reporting groups
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Reporting group title |
Tacrolimus cream 0.1%
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tacrolimus cream 0.1%
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Reporting group description |
- | ||
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End point title |
Pharmacokinetic whole blood tacrolimus concentrations [1] | ||||||||||||||||||||||||||||||||||||
End point description |
The analysis population is the pharmacokinetic set, which consisted of all participants from the Safety Set whose profile data were adequate for the calculation of the primary pharmacokinetic parameters.
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End point type |
Primary
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End point timeframe |
Day 29 (predose, hours 1, 2, 4, 6, 8, 12, 14 postdose) to Day 35 (postdose)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Maximum observed whole blood tacrolimus concentration (Cmax) [2] | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Primary
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End point timeframe |
Days 29-35
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum observed whole blood tacrolimus concentration from t=0 hour (time of morning dosing) through 12 hours post dose (t=12 hour) (Cmax0-tau) [3] | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Primary
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End point timeframe |
Days 29-35
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Minimum observed whole blood tacrolimus concentration from t=0 hour (time of morning dosing) through 12 hours post dose (t=12 hour) (Cmin0-tau) [4] | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Primary
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End point timeframe |
Days 29-35
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time of the maximum whole blood tacrolimus concentration (tmax) [5] | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Primary
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End point timeframe |
Days 29-35
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Average whole blood tacrolimus concentration over the morning dosing interval, i.e. from t=0 hour (time of morning dosing) through 12 hours post dose (t=12 hour) (Cavg0-tau) [6] | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Primary
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End point timeframe |
Days 29-35
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area under the whole blood tacrolimus concentration-time curve over the morning dosing interval; i.e., from t=0 hour (time of morning dosing) through 12 hours post dose (t=12 hour) (AUC0-tau) [7] | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Primary
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End point timeframe |
Days 29-35
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Safety as assessed by adverse events (AEs), clinical laboratory tests, vital signs, and physical examination [8] | ||||||||||||||||||
End point description |
Safety is monitored by collecting AEs, which include abnormal laboratory tests, vital signs or physical examination data that were defined as an AE if the abnormality induced clinical signs or symptoms, required diagnostic evaluation, therapeutic intervention, interruption or discontinuation of study medication or was clinically significant in the investigator's opinion. A treatment-emergent adverse event (TEAE) was defined as an AE occurring from the first dose day of study drug to the last dose day of study drug with onset or worsening after the first study drug application.
The analysis population is the Safety Set, which consisted of all participants who were administered any amount of tacrolimus cream 0.1%.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to 7 days after last dose of study drug
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was written with no planned statistical analyses (statistical hypothesis testing) to be performed for any endpoints due to the simple design (i.e., one treatment group) and purpose of the study. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Tacrolimus predose concentration at the end of the previous dosing interval (Ctrough) | ||||||||||||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 1, 8, 15, 22 and 29
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Average whole blood tacrolimus concentration from t=0 hour (time of morning dosing) through 24 hours post dose (t=24 hour) (Cavg0-24) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to last measurable concentration of the study drug (tlast) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Area under the whole blood tacrolimus concentration-time curve from t=0 hour (time of morning dosing) through 24 hours post dose (t=24 hour) (AUC0-24) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Peak-to-trough ratio over the 12 hours after the dose (PTRtau) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Difference in extreme concentrations (Cmax0-tau, Cmin0-tau) relative to the average concentration (Cavg0-tau) over the morning dosing interval (FLCTN0-tau) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Elimination rate constant (Kel) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Area under the whole blood tacrolimus concentration-time curve from t=0 hour (time of morning dosing) through time of last measurable concentration of tacrolimus (AUClast) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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End point title |
Area under the whole blood tacrolimus concentration-time curve from t=0 hour (time of morning dosing) extrapolated to infinity (AUC0-inf) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
Due to an insufficient number of measurable samples, AUC0-inf was assumed to be unreliable; hence, the value was not calculated.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| Notes [9] - Insufficient number of measurable samples. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal half life (t1/2) | ||||||||
End point description |
The analysis population is the pharmacokinetic set.
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End point type |
Secondary
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End point timeframe |
Days 29-35
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug up to 7 days after last dose of study drug
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
8.1
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Reporting groups
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Reporting group title |
Tacrolimus cream 0.1%
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Jun 2006 |
The original study protocol dated February 2, 2006 was amended once on June 14, 2006 (Latvia-specific) in order to provide required text per European Regulatory guidelines with respect to concomitant medication administration, adverse event reporting, study timelines and drug supplies, administrative and regulatory considerations. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
