Study of Asenapine in Elderly Subjects With Psychosis (A7501021)(P05717)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00281320
• Collaborator: (none)
• Enrollment: 122
• Arms: 2
• Duration (Months): 34

Study Details

Study Description

Brief Summary

This study evaluates the safety and tolerability of Asenapine in elderly patients with psychosis.

Condition or Disease	Intervention/Treatment	Phase
Psychosis	Drug: Asenapine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Parallel Group, Multiple Dose, 6-Week Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Asenapine in Elderly Subjects With Psychosis.
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Asenapine 2-10 mg BID Dose titration from 2 mg to 5 mg to 10 mg twice daily (BID)	Drug: Asenapine; Asenapine 2 mg twice daily (BID) on Days 1 and 2, 5 mg BID on Days 3 and 4, followed by 10 mg BID on Day 5 through the end of the trial (Week 6); or Asenapine 5 mg BID on Days 1 to 4 followed by 10 mg BID on Day 5 through the end of the trial (Week 6).; Other Names: Saphris
Experimental: Asenapine 5-10mg BID Dose titration from 5 mg to 10 mg BID	Drug: Asenapine; Asenapine 2 mg twice daily (BID) on Days 1 and 2, 5 mg BID on Days 3 and 4, followed by 10 mg BID on Day 5 through the end of the trial (Week 6); or Asenapine 5 mg BID on Days 1 to 4 followed by 10 mg BID on Day 5 through the end of the trial (Week 6).; Other Names: Saphris

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced an Adverse Event [Up to Day 42 (treatment period)]

   Participants who experienced treatment-emergent adverse events, defined as newly reported events after baseline or events reported to have worsened in severity since baseline (from the date of informed consent to the last dose day + 7 days for non-serious adverse events and 30 days for serious adverse events).

2. Number of Participants Who Discontinued Because of an Adverse Event [up to 30 days after study medication stop date]

   Discontinuations due to treatment-emergent adverse events starting on or after Day1 and up to 7 days after study medication stop date (30 days for serious adverse events).

3. Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Tmax [Day 4 or 8]

   Tmax defined as time to peak concentration.

4. Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis,Cmax [Day 4 or 8]

   Cmax defined as peak concentration.

5. Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis , Dn-Cmax [Day 4 or 8]

   dn-Cmax is defined as dose normalized peak concentration.

6. Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Cmin [Day 4 or 8]

   Cmin defined as pre-dose concentration.

7. Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, AUC 0-12 [Day 4 or 8]

   AUC 0-12 defined as area-under-the-curve from zero to time point 12 hours.

8. Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Dn-AUC 0-12 [Day 4 or 8]

   dn-AUC 0-12 defined as dose-normalized area-under-the-curve from zero to time point 12 hours.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Elderly subjects with psychosis

Exclusion Criteria:

• Have an uncontrolled, unstable clinically significant

medical condition.

• Have an established diagnosis of dementia

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00281320
• Other Study ID Numbers: P05717; A7501021
• First Posted: Jan 24, 2006
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Psychotic Disorders; Mental Disorders; Asenapine

Study Results

Participant Flow

Arm/Group Title	Asenapine 2-10 mg Twice Daily (BID)	Asenapine 5-10 mg BID
Arm/Group Description	Asenapine 2 mg twice daily (BID) on Days 1 and 2, 5 mg BID on Days 3 and 4, followed by 10 mg BID on Day 5 through the end of the trial (Week 6)	Asenapine 5 mg BID on Days 1 to 4 followed by 10 mg BID on Day 5 through the end of the trial (Week 6)
Period Title: Overall Study
STARTED	61	61
COMPLETED	36	40
NOT COMPLETED	25	21

Baseline Characteristics

Arm/Group Title	Asenapine 2-10 mg BID	Asenapine 5-10 mg BID	Total
Arm/Group Description	Asenapine 2 mg twice daily (BID) on Days 1 and 2, 5 mg BID on Days 3 and 4, followed by 10 mg BID on Day 5 through the end of the trial (Week 6)	Asenapine 5 mg twice daily (BID) on Days 1 to 4 followed by 10 mg BID on Day 5 through the end of the trial (Week 6)	Total of all reporting groups
Overall Participants	61	61	122
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.5 (4.6)	72.0 (5.8)	71.2 (5.2)
Sex: Female, Male (Count of Participants)
Female	41 67.2%	47 77%	88 72.1%
Male	20 32.8%	14 23%	34 27.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced an Adverse Event
Description	Participants who experienced treatment-emergent adverse events, defined as newly reported events after baseline or events reported to have worsened in severity since baseline (from the date of informed consent to the last dose day + 7 days for non-serious adverse events and 30 days for serious adverse events).
Time Frame	Up to Day 42 (treatment period)

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Asenapine 2-10 mg Twice Daily (BID)	Asenapine 5-10 mg BID
Arm/Group Description	Asenapine 2 mg twice daily (BID) on Days 1 and 2, 5 mg BID on Days 3 and 4, followed by 10 mg BID on Days 5 through the end of the trial (Week 6)	Asenapine 5 mg BID on Days 1 to 4 followed by 10 mg BID on Days 5 through the end of the trial (Week 6)
Measure Participants	61	61
Number [Participants]	44 72.1%	44 72.1%

2. Primary Outcome

Title	Number of Participants Who Discontinued Because of an Adverse Event
Description	Discontinuations due to treatment-emergent adverse events starting on or after Day1 and up to 7 days after study medication stop date (30 days for serious adverse events).
Time Frame	up to 30 days after study medication stop date

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Asenapine 2-10 mg Twice Daily (BID)	Asenapine 5-10 mg BID
Arm/Group Description	Asenapine 2 mg twice daily (BID) on Days 1 and 2, 5 mg BID on Days 3 and 4, followed by 10 mg BID on Days 5 through the end of the trial (Week 6)	Asenapine 5 mg BID on Days 1 to 4 followed by 10 mg BID on Days 5 through the end of the trial (Week 6)
Measure Participants	61	61
Number [participants]	12 19.7%	9 14.8%

3. Primary Outcome

Title	Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Tmax
Description	Tmax defined as time to peak concentration.
Time Frame	Day 4 or 8

Outcome Measure Data

Analysis Population Description

All-Subjects-Pharmacokinetically-Evaluable Group defined as all subjects for which at least one pharmacokinetic parameter could be calculated and who did not have any protocol violations interfering with pharmacokinetics.

Arm/Group Title	Asenapine 5mg BID Day 4	Asenapine 10mg BID Day 8
Arm/Group Description	Pharmacokinetic parameter of asepanine for Day 4.	Pharmacokinetic parameter of asepanine for Day 8.
Measure Participants	87	60
Median (Full Range) [hours]	1.00	1.06

4. Primary Outcome

Title	Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis,Cmax
Description	Cmax defined as peak concentration.
Time Frame	Day 4 or 8

Outcome Measure Data

Analysis Population Description

All-Subjects-Pharmacokinetically-Evaluable Group defined as all subjects for which at least one pharmacokinetic parameter could be calculated and who did not have any protocol violations interfering with pharmacokinetics.

Arm/Group Title	Asenapine 5mg BID Day 4	Asenapine 10mg BID Day 8
Arm/Group Description	Pharmacokinetic parameter of asepanine for Day 4.	Pharmacokinetic parameter of asepanine for Day 8.
Measure Participants	87	60
Mean (Standard Deviation) [ng/mL]	6.01 (3.89)	10.3 (6.71)

5. Primary Outcome

Title	Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis , Dn-Cmax
Description	dn-Cmax is defined as dose normalized peak concentration.
Time Frame	Day 4 or 8

Outcome Measure Data

Analysis Population Description

All-Subjects-Pharmacokinetically-Evaluable Group defined as all subjects for which at least one pharmacokinetic parameter could be calculated and who did not have any protocol violations interfering with pharmacokinetics.

Arm/Group Title	Asenapine 5mg BID Day 4	Asenapine 10mg BID Day 8
Arm/Group Description	Pharmacokinetic parameter of asepanine for Day 4.	Pharmacokinetic parameter of asepanine for Day 8.
Measure Participants	87	60
Mean (Standard Deviation) [ng/mL/mg]	1.20 (0.778)	1.03 (0.671)

6. Primary Outcome

Title	Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Cmin
Description	Cmin defined as pre-dose concentration.
Time Frame	Day 4 or 8

Outcome Measure Data

Analysis Population Description

All-Subjects-Pharmacokinetically-Evaluable Group defined as all subjects for which at least one pharmacokinetic parameter could be calculated and who did not have any protocol violations interfering with pharmacokinetics.

Arm/Group Title	Asenapine 5mg BID Day 4	Asenapine 10mg BID Day 8
Arm/Group Description	Pharmacokinetic parameters of asepanine for Day 4.	Pharmacokinetic parameters of asepanine for Day 8.
Measure Participants	86	60
Mean (Standard Deviation) [ng/mL]	2.28 (1.87)	4.06 (2.70)

7. Primary Outcome

Title	Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, AUC 0-12
Description	AUC 0-12 defined as area-under-the-curve from zero to time point 12 hours.
Time Frame	Day 4 or 8

Outcome Measure Data

Analysis Population Description

All-Subjects-Pharmacokinetically-Evaluable Group defined as all subjects for which at least one pharmacokinetic parameter could be calculated and who did not have any protocol violations interfering with pharmacokinetics.

Arm/Group Title	Asenapine 5mg BID Day 4	Asenapine 10mg BID Day 8
Arm/Group Description	Pharmacokinetic parameter of asenapine for Day 4.	Pharmacokinetic parameter of asenapine for Day 8.
Measure Participants	87	60
Mean (Standard Deviation) [ng*h/mL]	38.6 (21.1)	70.3 (41.8)

8. Primary Outcome

Title	Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Dn-AUC 0-12
Description	dn-AUC 0-12 defined as dose-normalized area-under-the-curve from zero to time point 12 hours.
Time Frame	Day 4 or 8

Outcome Measure Data

Analysis Population Description

All-Subjects-Pharmacokinetically-Evaluable Group defined as all subjects for which at least one pharmacokinetic parameter could be calculated and who did not have any protocol violations interfering with pharmacokinetics.

Arm/Group Title	Asenapine 5mg BID Day 4	Asenapine 10mg BID Day 8
Arm/Group Description	Pharmacokinetic parameter of asenapine for Day 4.	Pharmacokinetic parameter of asenapine for Day 8.
Measure Participants	87	60
Mean (Standard Deviation) [ng*h/mL/mg]	7.72 (4.22)	7.03 (4.18)

Adverse Events

Arm/Group Title	Asenapine 2-10mg BID		Asenapine 5-10mg BID
Arm/Group Description
All Cause Mortality
	Asenapine 2-10mg BID		Asenapine 5-10mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asenapine 2-10mg BID		Asenapine 5-10mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/61 (9.8%)		3/61 (4.9%)
Cardiac disorders
Cardio-respiratory arrest	1/61 (1.6%)	1	0/61 (0%)	0
Ventricular extrasystoles	0/61 (0%)	0	1/61 (1.6%)	1
Injury, poisoning and procedural complications
Fall	1/61 (1.6%)	1	0/61 (0%)	0
Hip fracture	1/61 (1.6%)	1	0/61 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to pleura	1/61 (1.6%)	1	0/61 (0%)	0
Nervous system disorders
Extrapyramidal disorder	1/61 (1.6%)	1	0/61 (0%)	0
Psychiatric disorders
Mania	0/61 (0%)	0	1/61 (1.6%)	1
Mental status changes	1/61 (1.6%)	1	0/61 (0%)	0
Psychotic disorder	1/61 (1.6%)	1	0/61 (0%)	0
Schizophrenia	0/61 (0%)	0	1/61 (1.6%)	1
Renal and urinary disorders
Azotaemia	1/61 (1.6%)	1	0/61 (0%)	0
Other (Not Including Serious) Adverse Events
	Asenapine 2-10mg BID		Asenapine 5-10mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/61 (34.4%)		21/61 (34.4%)
General disorders
Asthenia	4/61 (6.6%)	4	2/61 (3.3%)	2
Infections and infestations
Urinary tract infection	4/61 (6.6%)	4	0/61 (0%)	0
Investigations
Blood pressure increased	0/61 (0%)	0	5/61 (8.2%)	7
Nervous system disorders
Dizziness	4/61 (6.6%)	4	2/61 (3.3%)	3
Headache	4/61 (6.6%)	4	4/61 (6.6%)	4
Parkinsonism	1/61 (1.6%)	1	5/61 (8.2%)	6
Somnolence	5/61 (8.2%)	6	3/61 (4.9%)	5
Psychiatric disorders
Anxiety	0/61 (0%)	0	4/61 (6.6%)	4
Vascular disorders
Hypertension	7/61 (11.5%)	11	3/61 (4.9%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Institution will provide manuscripts, abstracts, or the full text of any other intended disclosure to the sponsor at least 30 days prior to submission for publication or other disclosure. If any patent action is required to protect intellectual property rights, Institution agrees to delay the disclosure for a period not to exceed and additional 60 days. Institution will, on request, remove any previously undisclosed Confidential Information (other than study results) before disclosure.