Clinical Trial Results:
An Open Label Evaluation of the Adrenal Suppression Potential and Trough Plasma Concentrations of Cortexolone 17α-Propionate (CB-03-01) Cream Applied Every 12 Hours for Two Weeks in Subjects 9 to <12 Years of Age with Acne Vulgaris
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Summary
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EudraCT number |
2016-000616-15 |
Trial protocol |
PL |
Global end of trial date |
21 Mar 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Jul 2020
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First version publication date |
15 Jul 2020
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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 |
CB-03-01/28
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02720627 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Cassiopea S.p.A.
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Sponsor organisation address |
Via C. Colombo 1, Lainate, Italy, 20045
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Public contact |
R&D Department, Cassiopea S.P.A., +39 0286891124,
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Scientific contact |
R&D Department, Cassiopea S.P.A., +39 0286891124,
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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 |
16 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Mar 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Mar 2018
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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 objectives of this study are to determine a) the adrenal suppression potential and b) the trough plasma concentrations associated with topical application of CB-03-01 cream, 1% in subjects with acne vulgaris.
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Protection of trial subjects |
The study protocol, consent/assent form, participant recruitment materials/process and other relevant study documents were submitted to involved Ethic Committee (ECs)/Institutional Review Boards (IRBs) and approved prior to study initiation.
This study was conducted in accordance with principles of the Declaration of Helsinki, with the current Good Clinical Practice guidelines and with other applicable regulations. The investigators and all study staff conducted the study in compliance with the study protocol.
Interested individuals, male and female subjects 9 to <12 years of age, accompanied by their parent or legal guardian were given an opportunity to discuss the activities involved in study participation with the site staff and the principal investigator. An IRB/EC-approved informed consent/assent form and subject instruction sheet was given to the potential subject and his/her parent or legal guardian and an opportunity afforded to read the consent/assent form and ask questions. Those individuals interested in participation were requested to sign the informed consent/assent form prior to the performance of any study-related procedures.
The rights, safety, and wellbeing of the study subjects were the most important considerations and prevailed over the interests of science and society.
Identifying any untoward medical occurrence and timely and complete reporting of all AEs was aimed at the most efficient protection of the safety of study subjects.
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Background therapy |
No background therapy is planned, the only administered drug (apart CB-03-01) was cosyntropin for HPA stimulation. | ||
Evidence for comparator |
No comparators were used in the study. | ||
Actual start date of recruitment |
28 Oct 2016
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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 |
Poland: 18
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Country: Number of subjects enrolled |
United States: 9
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Worldwide total number of subjects |
27
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EEA total number of subjects |
18
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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) |
27
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Adolescents (12-17 years) |
0
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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 |
Patients recruited by investigators in their research sites (US, Poland) from the database or by means of website advertisement or reference from other doctors. Patients underwent screening procedures and were required to meet all the inclusion criteria and none of the exclusion criteria. Recruitment period throughout the study course. | ||||||
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Pre-assignment
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Screening details |
38 subjects screened, 27 subjects enrolled into the study, 11 subjects were screen failures. Reasons for screen failures: did not meet all inclusion criteria (6), withdrawal by subject (2), met at least one exclusion criteria (1), withdrawal due to medical history Sponsor suggestion (1) and investigator decision (1). 27 subjects completed the study | ||||||
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Pre-assignment period milestones
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Number of subjects started |
27 | ||||||
Number of subjects completed |
27 | ||||||
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Period 1
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Period 1 title |
Overall Trial (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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CB-03-01 cream | ||||||
Arm description |
Eligible subjects were dispensed CB-03-01 cream, 1% at baseline visit and provided with additional labeled test article during the study period. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Clascoterone cream 1%
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Investigational medicinal product code |
CB-03-01 cream 1%
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Other name |
Cortexolone 17α-propionate cream 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 |
All eligible subjects were dispensed CB-03-01 cream, 1%. The subjects and his/her parent/guardian were instructed to apply 2 gr of the test article per application to the face and trunk every 12 hours for two weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
Safety Population - includes all enrolled subjects who were dispensed and applied at least one dose of the test article. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Evaluable Population
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Evaluable population included those subjects in the Safety population who had both Screening and Day 14 serum cortisol data (pre- and post-cosyntropin stimulation) and met the following criteria:
-Met all inclusion/exclusion criteria, including normal response to cosyntropin stimulation defined as a Screening CST with a 30-minute post-stimulation cortisol level of > 18 μg/dL.
-Screening and Day 14 CST were conducted between 7-9 AM.
-Day 14 CST was conducted within ±1 hour of the Screening CST.
-Applied at least 80% of expected applications and applied the final dose no more than 14 hours prior to the start of the CST.
-Had not taken or applied any medications that may interfere with HPA axis function.
-Did not have any other significant protocol deviations.
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Subject analysis set title |
Pharmacokinetic Population
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The PK population included those subjects in the Safety population who had at least an 80% dose compliance based on number of applications, had at least one post-baseline PK blood draw within ±2 days of the scheduled visit at Days 7 and 14, and did not have any significant protocol deviations.
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End points reporting groups
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Reporting group title |
CB-03-01 cream
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Reporting group description |
Eligible subjects were dispensed CB-03-01 cream, 1% at baseline visit and provided with additional labeled test article during the study period. | ||
Subject analysis set title |
Evaluable Population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The Evaluable population included those subjects in the Safety population who had both Screening and Day 14 serum cortisol data (pre- and post-cosyntropin stimulation) and met the following criteria:
-Met all inclusion/exclusion criteria, including normal response to cosyntropin stimulation defined as a Screening CST with a 30-minute post-stimulation cortisol level of > 18 μg/dL.
-Screening and Day 14 CST were conducted between 7-9 AM.
-Day 14 CST was conducted within ±1 hour of the Screening CST.
-Applied at least 80% of expected applications and applied the final dose no more than 14 hours prior to the start of the CST.
-Had not taken or applied any medications that may interfere with HPA axis function.
-Did not have any other significant protocol deviations.
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Subject analysis set title |
Pharmacokinetic Population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The PK population included those subjects in the Safety population who had at least an 80% dose compliance based on number of applications, had at least one post-baseline PK blood draw within ±2 days of the scheduled visit at Days 7 and 14, and did not have any significant protocol deviations.
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End point title |
HPA Axis Response at Day 14 [1] | ||||||||||
End point description |
HPA axis responses to cosyntropin were dichotomized to normal and abnormal.
An abnormal HPA axis response was defined as a 30-minute post-stimulation serum cortisol level of ≤18 μg/dL at Day 14.
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End point type |
Primary
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End point timeframe |
Cosyntropin stimulation testing was performed at Screening and Day 14 and approximately four weeks post-treatment if a subject’s laboratory results at Day 14 showed an abnormal HPA axis response (HPA suppression).
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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: The proportion of subjects manifesting laboratory based evidence of adrenal suppression at Day 14 was presented along with 95% confidence intervals (0.0; 20.2) for the Evaluable population. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Serum Cortisol Levels [2] | ||||||||||||||||||||||||||
End point description |
Serum cortisol samples were analyzed via a validated method.
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End point type |
Primary
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End point timeframe |
Measurement of serum cortisol concentrations after stimulation of the adrenal cortex with Cosyntropin (CST) was performed at Screening and Day 14 (or end of study) and four weeks post-treatment in case of HPA suppression result at Day 14.
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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: The observed serum cortisol levels (pre- and post-cosyntropin stimulation) and the changes in serum cortisol levels after stimulation at Screening, Day 14, and, if any, at follow-up visits were summarized using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Trough Concentrations of Clascoterone and Cortexolone [3] | ||||||||||||||||||||||||
End point description |
A second primary objective of this study was to determine the trough plasma concentrations associated with topical application of CB-03-01 cream, 1% in subjects with acne vulgaris. A validated method was used for the accurate determination of Clascoterone and Cortexolone concentrations in human plasma in all study samples.
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End point type |
Primary
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End point timeframe |
Blood samples were collected for morning trough concentrations of Clascoterone and Cortexolone in
plasma at Screening, Day 1 (pre-dose), Day, 7 and Day 14.
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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: Morning trough concentrations (C12) of clascoterone and cortexolone in plasma at Screening, Day 1, Day 7 and Day 14 were summarized for the PK population using geometric mean, coefficient of variation in addition to n, mean, median, standard deviation, minimum and maximum. Individual trough concentrations of clascoterone and cortexolone in plasma across visits were plotted. Individual average trough concentrations of clascoterone and cortexolone were also plotted by adrenal suppression status |
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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 |
Screening, Baseline, Day 7 and Day 14. The investigator instructed the subject to report any AEs that might have occurred during the study. At each visit, the investigator asked the subject about any change in his/her condition.
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Adverse event reporting additional description |
All AEs had to be recorded on the AE CRF. AEs should have been followed to resolution or stabilization (if possible), and reported as serious adverse events (SAEs) if they became serious.
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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 |
18.1
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
The study involved 1 arm, thus all study participants are considered as one group. | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
