Psychosis
Conditions
Brief summary
This study evaluates the safety and tolerability of Asenapine in elderly patients with psychosis.
Interventions
DRUGAsenapine
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).
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asenapine 2-10 mg 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) | 61 |
| Asenapine 5-10 mg BID 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) | 61 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 9 |
| Overall Study | Lack of Efficacy | 4 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Asenapine 2-10 mg BID | Asenapine 5-10 mg BID | Total |
|---|---|---|---|
| Age, Continuous | 70.5 years STANDARD_DEVIATION 4.6 | 72.0 years STANDARD_DEVIATION 5.8 | 71.2 years STANDARD_DEVIATION 5.2 |
| Sex: Female, Male Female | 41 Participants | 47 Participants | 88 Participants |
| Sex: Female, Male Male | 20 Participants | 14 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 61 | 21 / 61 |
| serious Total, serious adverse events | 6 / 61 | 3 / 61 |
Outcome results
Primary
Number of Participants Who Discontinued Because of an Adverse Event
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
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | Number of Participants Who Discontinued Because of an Adverse Event | 12 participants |
| Asenapine 5-10 mg BID | Number of Participants Who Discontinued Because of an Adverse Event | 9 participants |
Primary
Number of Participants Who Experienced an Adverse Event
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)
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | Number of Participants Who Experienced an Adverse Event | 44 Participants |
| Asenapine 5-10 mg BID | Number of Participants Who Experienced an Adverse Event | 44 Participants |
Primary
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, AUC 0-12
AUC 0-12 defined as area-under-the-curve from zero to time point 12 hours.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | 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 |
| Asenapine 5-10 mg BID | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, AUC 0-12 | 70.3 ng*h/mL | Standard Deviation 41.8 |
Primary
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis,Cmax
Cmax defined as peak concentration.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis,Cmax | 6.01 ng/mL | Standard Deviation 3.89 |
| Asenapine 5-10 mg BID | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis,Cmax | 10.3 ng/mL | Standard Deviation 6.71 |
Primary
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Cmin
Cmin defined as pre-dose concentration.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Cmin | 2.28 ng/mL | Standard Deviation 1.87 |
| Asenapine 5-10 mg BID | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Cmin | 4.06 ng/mL | Standard Deviation 2.7 |
Primary
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Dn-AUC 0-12
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | 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 |
| Asenapine 5-10 mg BID | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Dn-AUC 0-12 | 7.03 ng*h/mL/mg | Standard Deviation 4.18 |
Primary
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis , Dn-Cmax
dn-Cmax is defined as dose normalized peak concentration.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | 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 |
| Asenapine 5-10 mg BID | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis , Dn-Cmax | 1.03 ng/mL/mg | Standard Deviation 0.671 |
Primary
Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Tmax
Tmax defined as time to peak concentration.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asenapine 2-10 mg Twice Daily (BID) | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Tmax | 1.00 hours |
| Asenapine 5-10 mg BID | Pharmacokinetics of Asenapine up to Doses of 10 mg BID in Elderly Subjects With Psychosis, Tmax | 1.06 hours |