Trial Outcomes & Findings for Study of Asenapine in Elderly Subjects With Psychosis (A7501021)(P05717) (NCT NCT00281320)

NCT ID: NCT00281320

Last Updated: 2022-02-09

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 122 participants
• Primary outcome timeframe: Up to Day 42 (treatment period)
• Results posted on: 2022-02-09

Participant Flow

Participant milestones

Measure	Asenapine 2-10 mg Twice Daily (BID) 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 5-10 mg BID 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)
Overall Study STARTED	61	61
Overall Study COMPLETED	36	40
Overall Study NOT COMPLETED	25	21

Reasons for withdrawal

Measure	Asenapine 2-10 mg Twice Daily (BID) 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 5-10 mg BID 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)
Overall Study Adverse Event	12	9
Overall Study Lack of Efficacy	4	3
Overall Study Withdrawal by Subject	5	6
Overall Study Lost to Follow-up	1	2
Overall Study Other	3	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Asenapine 2-10 mg BID n=61 Participants 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 5-10 mg BID n=61 Participants 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 n=122 Participants Total of all reporting groups
Age, Continuous	70.5 years STANDARD_DEVIATION 4.6 • n=5 Participants	72.0 years STANDARD_DEVIATION 5.8 • n=7 Participants	71.2 years STANDARD_DEVIATION 5.2 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	47 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 42 (treatment period)

Population: Per protocol

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).

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=61 Participants 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 5-10 mg BID n=61 Participants 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)
Number of Participants Who Experienced an Adverse Event	44 Participants	44 Participants

PRIMARY outcome

Timeframe: up to 30 days after study medication stop date

Population: Per protocol

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).

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=61 Participants 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 5-10 mg BID n=61 Participants 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)
Number of Participants Who Discontinued Because of an Adverse Event	12 participants	9 participants

PRIMARY outcome

Timeframe: Day 4 or 8

Population: 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.

Tmax defined as time to peak concentration.

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=87 Participants 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 5-10 mg BID n=60 Participants 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)
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Tmax	1.00 hours Interval 0.417 to 4.23	1.06 hours Interval 0.417 to 4.08

PRIMARY outcome

Timeframe: Day 4 or 8

Population: 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.

Cmax defined as peak concentration.

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=87 Participants 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 5-10 mg BID n=60 Participants 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)
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis,Cmax	6.01 ng/mL Standard Deviation 3.89	10.3 ng/mL Standard Deviation 6.71

PRIMARY outcome

Timeframe: Day 4 or 8

Population: 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.

dn-Cmax is defined as dose normalized peak concentration.

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=87 Participants 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 5-10 mg BID n=60 Participants 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)
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis , Dn-Cmax	1.20 ng/mL/mg Standard Deviation 0.778	1.03 ng/mL/mg Standard Deviation 0.671

PRIMARY outcome

Timeframe: Day 4 or 8

Population: 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.

Cmin defined as pre-dose concentration.

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=86 Participants 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 5-10 mg BID n=60 Participants 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)
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Cmin	2.28 ng/mL Standard Deviation 1.87	4.06 ng/mL Standard Deviation 2.70

PRIMARY outcome

Timeframe: Day 4 or 8

Population: 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.

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

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=87 Participants 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 5-10 mg BID n=60 Participants 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)
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, AUC 0-12	38.6 ng*h/mL Standard Deviation 21.1	70.3 ng*h/mL Standard Deviation 41.8

PRIMARY outcome

Timeframe: Day 4 or 8

Population: 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.

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

Outcome measures

Measure	Asenapine 2-10 mg Twice Daily (BID) n=87 Participants 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 5-10 mg BID n=60 Participants 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)
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Dn-AUC 0-12	7.72 ng*h/mL/mg Standard Deviation 4.22	7.03 ng*h/mL/mg Standard Deviation 4.18

Adverse Events

Asenapine 2-10mg BID

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Asenapine 5-10mg BID

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Asenapine 2-10mg BID n=61 participants at risk	Asenapine 5-10mg BID n=61 participants at risk
Cardiac disorders Cardio-respiratory arrest	1.6% 1/61 • Number of events 1	0.00% 0/61
Cardiac disorders Ventricular extrasystoles	0.00% 0/61	1.6% 1/61 • Number of events 1
Injury, poisoning and procedural complications Fall	1.6% 1/61 • Number of events 1	0.00% 0/61
Injury, poisoning and procedural complications Hip fracture	1.6% 1/61 • Number of events 1	0.00% 0/61
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to pleura	1.6% 1/61 • Number of events 1	0.00% 0/61
Nervous system disorders Extrapyramidal disorder	1.6% 1/61 • Number of events 1	0.00% 0/61
Psychiatric disorders Mania	0.00% 0/61	1.6% 1/61 • Number of events 1
Psychiatric disorders Mental status changes	1.6% 1/61 • Number of events 1	0.00% 0/61
Psychiatric disorders Psychotic disorder	1.6% 1/61 • Number of events 1	0.00% 0/61
Psychiatric disorders Schizophrenia	0.00% 0/61	1.6% 1/61 • Number of events 1
Renal and urinary disorders Azotaemia	1.6% 1/61 • Number of events 1	0.00% 0/61

Other adverse events

Measure	Asenapine 2-10mg BID n=61 participants at risk	Asenapine 5-10mg BID n=61 participants at risk
General disorders Asthenia	6.6% 4/61 • Number of events 4	3.3% 2/61 • Number of events 2
Infections and infestations Urinary tract infection	6.6% 4/61 • Number of events 4	0.00% 0/61
Investigations Blood pressure increased	0.00% 0/61	8.2% 5/61 • Number of events 7
Nervous system disorders Dizziness	6.6% 4/61 • Number of events 4	3.3% 2/61 • Number of events 3
Nervous system disorders Headache	6.6% 4/61 • Number of events 4	6.6% 4/61 • Number of events 4
Nervous system disorders Parkinsonism	1.6% 1/61 • Number of events 1	8.2% 5/61 • Number of events 6
Nervous system disorders Somnolence	8.2% 5/61 • Number of events 6	4.9% 3/61 • Number of events 5
Psychiatric disorders Anxiety	0.00% 0/61	6.6% 4/61 • Number of events 4
Vascular disorders Hypertension	11.5% 7/61 • Number of events 11	4.9% 3/61 • Number of events 3

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER