Flexible Dose, Long-term Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05897)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01190267
• Collaborator: (none)
• Enrollment: 204
• Arm: 1
• Actual Duration (Months): 36.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia, Paranoid; Schizophrenia, Disorganized; Schizophrenia, Undifferentiated	Drug: asenapine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 204 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-week, Multi-center, Open-label, Flexible Dose, Long-term Safety Trial of Asenapine in Adolescent Subjects With Schizophrenia
• Actual Study Start Date: Sep 28, 2010
• Actual Primary Completion Date: Oct 7, 2013
• Actual Study Completion Date: Oct 7, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Asenapine All enrolled participants receive open-label asenapine 2.5 mg twice daily (BID) on Day 1-3, which is increased to 5.0 mg BID on Day 4 (dose can be increased earlier at the investigator's discretion). Asenapine dosing is flexible for the remainder of the 26-week open-label drug administration period, and can be adjusted to either 2.5 mg or 5.0 mg BID at the investigator's discretion, based on tolerability and/or symptomatology.

Drug: asenapine; asenapine 2.5 mg or 5.0 mg sublingual tablets, administered BID; Other Names: Saphris®, SCH 900274, Org 5222

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Treatment-Emergent Adverse Event (AE) During Extension Study [Up to 30 weeks]

   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.

2. Number of Participants Who Discontinued Study Drug During Extension Study Due to an AE [Up to 26 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Each participant must be between 12 and 17 years of age at the time of entry on this study, however, participants in the 8-week base study (P05896 [NCT01190254]) who reach 18 years of age while on P05896 may be enrolled in this extension study provided all other inclusion/exclusion criteria are met.

• Must have completed the 8-week efficacy and safety trial (P05896 [NCT01190254]) and, according to the investigator's judgment, would benefit from long-term treatment.

• Must have demonstrated an acceptable degree of compliance with trial medication, visits, and other requirements in the 8-week trial (P05896 [NCT01190254]), in the opinion of the investigator.

Exclusion Criteria:

• A female participant must not be pregnant and must not have the intention to become pregnant during the trial.

• A participant must not be at imminent risk of self-harm or harm to others.

• A participant must not currently be under involuntary inpatient commitment.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01190267
• Other Study ID Numbers: P05897; 2009-018038-12; MK-8274-021
• First Posted: Aug 27, 2010
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Schizophrenia; Schizophrenia, Disorganized; Schizophrenia, Paranoid; Asenapine

Study Results

Participant Flow

Arm/Group Title	Asenapine - Participants Who Were ≤17 Years Old	Asenapine - Participants Who Were 18 Years Old
Arm/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.	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.
Period Title: Overall Study
STARTED	196	8
COMPLETED	155	4
NOT COMPLETED	41	4

Baseline Characteristics

Arm/Group Title	Asenapine - Participants Who Were ≤17 Years Old	Asenapine - Participants Who Were 18 Years Old	Total
Arm/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.	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.	Total of all reporting groups
Overall Participants	196	8	204
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.3 (1.5)	18 (0)	15.4 (1.6)
Sex: Female, Male (Count of Participants)
Female	74 37.8%	4 50%	78 38.2%
Male	122 62.2%	4 50%	126 61.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Treatment-Emergent Adverse Event (AE) During Extension Study
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.
Time Frame	Up to 30 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of extension study medication

Arm/Group Title	Asenapine - Participants Who Were ≤17 Years Old	Asenapine - Participants Who Were 18 Years Old
Arm/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.	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.
Measure Participants	196	8
Number [participants]	114 58.2%	3 37.5%

2. Primary Outcome

Title	Number of Participants Who Discontinued Study Drug During Extension Study Due to an AE
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.
Time Frame	Up to 26 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of extension study medication

Arm/Group Title	Asenapine - Participants Who Were ≤17 Years Old	Asenapine - Participants Who Were 18 Years Old
Arm/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.	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.
Measure Participants	196	8
Number [participants]	10 5.1%	0 0%

Adverse Events

Time Frame	Up to 30 weeks
Adverse Event Reporting 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).
Arm/Group Title	Asenapine - Participants Who Were ≤17 Years Old		Asenapine - Participants Who Were 18 Years Old
Arm/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.		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.
All Cause Mortality
	Asenapine - Participants Who Were ≤17 Years Old		Asenapine - Participants Who Were 18 Years Old
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asenapine - Participants Who Were ≤17 Years Old		Asenapine - Participants Who Were 18 Years Old
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/196 (3.6%)		1/8 (12.5%)
General disorders
MULTI-ORGAN FAILURE	1/196 (0.5%)	1	0/8 (0%)	0
Psychiatric disorders
AGGRESSION	2/196 (1%)	2	0/8 (0%)	0
AGITATION	1/196 (0.5%)	1	0/8 (0%)	0
ANXIETY	1/196 (0.5%)	1	1/8 (12.5%)	1
SCHIZOPHRENIA	3/196 (1.5%)	3	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Asenapine - Participants Who Were ≤17 Years Old		Asenapine - Participants Who Were 18 Years Old
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/196 (30.1%)		3/8 (37.5%)
Eye disorders
VISION BLURRED	1/196 (0.5%)	1	1/8 (12.5%)	1
General disorders
FATIGUE	5/196 (2.6%)	5	1/8 (12.5%)	1
FEELING COLD	0/196 (0%)	0	1/8 (12.5%)	1
PAIN	1/196 (0.5%)	1	1/8 (12.5%)	1
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE	3/196 (1.5%)	4	1/8 (12.5%)	3
INJURY	0/196 (0%)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/196 (0%)	0	1/8 (12.5%)	1
Nervous system disorders
AKATHISIA	4/196 (2%)	4	1/8 (12.5%)	1
BRADYKINESIA	0/196 (0%)	0	1/8 (12.5%)	1
COGWHEEL RIGIDITY	0/196 (0%)	0	1/8 (12.5%)	1
HEADACHE	13/196 (6.6%)	18	0/8 (0%)	0
HYPOAESTHESIA	0/196 (0%)	0	1/8 (12.5%)	1
RESTING TREMOR	0/196 (0%)	0	1/8 (12.5%)	1
SEDATION	10/196 (5.1%)	11	1/8 (12.5%)	3
SOMNOLENCE	29/196 (14.8%)	36	0/8 (0%)	0
TREMOR	4/196 (2%)	4	1/8 (12.5%)	1
Psychiatric disorders
SUICIDAL IDEATION	3/196 (1.5%)	3	1/8 (12.5%)	2
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	1/196 (0.5%)	1	1/8 (12.5%)	1
UPPER RESPIRATORY TRACT CONGESTION	0/196 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
ACNE	1/196 (0.5%)	1	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

It is planned to first publish/present trial results together with the other sites, unless permission is obtained from Sponsor to publish separate results. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. If there is disagreement concerning appropriateness of the materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve disagreement prior to submission for publication.