Clinical Trial Results:
A 26-Week, Multi-Center, Open-Label, Flexible Dose, Long-Term Safety Trial of Asenapine in Adolescent Subjects with Schizophrenia
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Summary
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EudraCT number |
2009-018038-12 |
Trial protocol |
RO Outside EU/EEA |
Global end of trial date |
07 Oct 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Jun 2016
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First version publication date |
26 Jul 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 |
P05897
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01190267 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Merck Protocol number: MK-8274-021 | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Oct 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Oct 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Oct 2013
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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 |
This study is designed to evaluate whether asenapine, which is approved by the United States Food and Drug Administration (US FDA) for acute treatment of schizophrenia in adults, is generally safe and well tolerated in adolescents with schizophrenia. This is an extension of base study P05896 (NCT01190254), which means participants must have completed participation in the 8-week base study in order to qualify for this extension study P05897. Participants in this extension study will receive open-label asenapine for 26 weeks. Throughout the study, observations will be made on each participant at various times to assess the long-term safety, tolerability and efficacy of the study treatment.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure defined for this individual study was in place for the protection of trial subjects: For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Sep 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Bosnia and Herzegovina: 2
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Country: Number of subjects enrolled |
Colombia: 4
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Country: Number of subjects enrolled |
Romania: 4
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Country: Number of subjects enrolled |
Croatia: 4
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Country: Number of subjects enrolled |
India: 40
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Country: Number of subjects enrolled |
Korea, Republic of: 2
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Country: Number of subjects enrolled |
Mexico: 1
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Country: Number of subjects enrolled |
Russian Federation: 88
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Country: Number of subjects enrolled |
Serbia: 6
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Country: Number of subjects enrolled |
Ukraine: 17
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Country: Number of subjects enrolled |
United States: 33
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Country: Number of subjects enrolled |
South Africa: 3
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Worldwide total number of subjects |
204
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EEA total number of subjects |
8
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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) |
196
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Adults (18-64 years) |
8
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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 |
204 participants entered the study and received at least one dose of open-label trial medication. | ||||||||||||||||||||||||||||||
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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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Are arms mutually exclusive |
Yes
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Arm title
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Asenapine - Participants Who Were ≤17 Years Old | ||||||||||||||||||||||||||||||
Arm description |
In this extension study all participants received open-label asenapine 2.5 mg twice daily (BID) on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were ≤17 years old at entry into the extension study. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
asenapine
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Investigational medicinal product code |
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Other name |
Saphris®, SCH 900274, Org 5222
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
asenapine 2.5 mg or 5.0 mg sublingual tablets, administered BID
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Arm title
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Asenapine - Participants Who Were 18 Years Old | ||||||||||||||||||||||||||||||
Arm description |
In this extension study all participants received open-label asenapine 2.5 mg BID on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were 18 years old at entry into the extension study. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
asenapine
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Investigational medicinal product code |
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Other name |
Saphris®, SCH 900274, Org 5222
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
asenapine 2.5 mg or 5.0 mg sublingual tablets, administered BID
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Baseline characteristics reporting groups
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Reporting group title |
Asenapine - Participants Who Were ≤17 Years Old
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Reporting group description |
In this extension study all participants received open-label asenapine 2.5 mg twice daily (BID) on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were ≤17 years old at entry into the extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Asenapine - Participants Who Were 18 Years Old
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Reporting group description |
In this extension study all participants received open-label asenapine 2.5 mg BID on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were 18 years old at entry into the extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Asenapine - Participants Who Were ≤17 Years Old
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Reporting group description |
In this extension study all participants received open-label asenapine 2.5 mg twice daily (BID) on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were ≤17 years old at entry into the extension study. | ||
Reporting group title |
Asenapine - Participants Who Were 18 Years Old
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Reporting group description |
In this extension study all participants received open-label asenapine 2.5 mg BID on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were 18 years old at entry into the extension study. | ||
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End point title |
Number of Participants With a Treatment-Emergent Adverse Event (AE) During Extension Study [1] | |||||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was defined as a “treatment-emergent” AE if it was not present at the extension study baseline, or if it was present at the extension study baseline but worsened in severity compared to baseline during the extension study treatment period. Population for analysis was all participants who received at least one dose of extension study medication.
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End point type |
Primary
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End point timeframe |
Up to 30 weeks
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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: No hypothesis testing was planned for this endpoint. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Who Discontinued Study Drug During Extension Study Due to an AE [2] | |||||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Population for analysis was all participants who received at least one dose of extension study medication.
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End point type |
Primary
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End point timeframe |
Up to 26 weeks
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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: No hypothesis testing was planned for this endpoint. |
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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 |
Up to 30 weeks
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Adverse event reporting additional description |
The serious adverse events (SAEs) table includes all SAEs that occurred during this extension study. The Other AEs table includes only AEs in study that were “treatment-emergent” (i.e., not present at the extension study baseline, or present at the extension study baseline but worsened in severity compared to baseline during the extension study).
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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 |
16.0
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Reporting groups
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Reporting group title |
Asenapine - Participants Who Were ≤17 Years Old
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Reporting group description |
In this extension study all participants received open-label asenapine 2.5 mg BID on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were ≤17 years old at entry into the extension study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Asenapine - Participants Who Were 18 Years Old
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Reporting group description |
In this extension study all participants received open-label asenapine 2.5 mg BID on Day 1-3, which was increased to 5.0 mg BID on Day 4 (dose could be increased earlier). Asenapine dosing was flexible for the remainder of the 26-week open-label drug administration period, and could be adjusted to either 2.5 mg or 5.0 mg BID. Participants in this reporting group were 18 years old at entry into the extension study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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23 Sep 2011 |
Amendment 01: Primary reason for amendment was to incorporate revision to upper limit of age range for entry into study. |
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03 May 2012 |
Amendment 02: Primary reason for amendment was to incorporate revisions to requirements for final visit of preceding base study (P05896) and baseline visit of this extension study (P05897), list of efficacy endpoints, allowed concomitant medications/rescue therapy, list of closely monitored events, criteria for clinically important changes in safety measures and procedures for liver enzyme monitoring. |
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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 | |||
