Schizophrenia
Conditions
Keywords
schizophrenia, antipsychotics, dopamine D3/D2 antagonist
Brief summary
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of 3 fixed doses of MP-214 orally administered once daily to patients with schizophrenia. MP-214 tablets will be administered to patients starting at an initial dose, followed by up-titration to a fixed dose (low, medium or high) for 14 days.
Interventions
DRUGCariprazine 3 mg
DRUGCariprazine 6 mg
DRUGCariprazine 12.5 mg
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients meeting DSM-IV-TR criteria for schizophrenia * PANSS total score \<= 120 during the observation period * Patients who have been treated with oral antipsychotics within 4 weeks before informed consent * Patients whose consent is obtained from themselves in written form
Exclusion criteria
* Patients who have defined as any mental disorder other than Schizophrenia based on the criteria of DSM-IV-TR * History of drug or alcohol abuse * Concurrent Parkinson's disease * History of, or concurrent spastic disorders like epilepsy, cerebrovascular disease, anuresis or adynamic(= paralytic) ileus, malignant syndrome, diabetes, hepatic disorder * Patients who exhibit abnormalities on Physical Examination, have abnormal vital signs, ECG, or clinical laboratory values * Current cataract during the observation period * History of shock or anaphylactoid symptoms to drugs The information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Event and Adverse Drug Reaction | Up to 7 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14. |
| Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Day 14 (Last Observation Carried Forward; LOCF) | at baseline, and on Day 14 or a last observation carried forward (LOCF) | CGI-S is a 7-point scale to assess the global severity of the participant's illness. CGI-S scores range from 1 (normal, not ill at all) to 7 (extremely ill). |
| The Clinical Global Impression-Improvement (CGI-I) Score at Day 14 (Last Observation Carried Forward; LOCF) | on Day 14 or a last observation carried forward (LOCF) | CGI-I is a 7-point scale to assess the global improvement of the participant's illness relative to baseline. CGI-I scores range from 1 (very much improved) to 7 (very much worse). |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 14 (Last Observation Carried Forward; LOCF) | at baseline, and on Day 14 or a last observation carried forward (LOCF) | PANSS score is a 30-item rating scale to assess both the positive and negative symptom syndromes of patients with schizophrenia. Each item is scored on a 7-point scale, from 1 (absent) to 7 (extreme). The PANSS total score of the 30 PANSS items ranges from 30 to 210. High scores indicate greater severity of symptoms. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cariprazine 3 mg | 12 |
| Cariprazine 6 mg | 10 |
| Cariprazine 12.5 mg | 12 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Cariprazine 3 mg | Cariprazine 6 mg | Cariprazine 12.5 mg | Total |
|---|---|---|---|---|
| Age, Customized >=18 and =<30 years | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=31 and =<40 years | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Age, Customized >=41 and =<55 years | 6 Participants | 3 Participants | 5 Participants | 14 Participants |
| Age, Customized >55 years | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 8 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 12 | 9 / 10 | 11 / 12 |
| serious Total, serious adverse events | 3 / 12 | 1 / 10 | 2 / 12 |
Outcome results
Primary
Number of Participants With Adverse Event and Adverse Drug Reaction
Time frame: Up to 7 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cariprazine 3 mg | Number of Participants With Adverse Event and Adverse Drug Reaction | Number of Participants With Adverse event | 9 Participants |
| Cariprazine 3 mg | Number of Participants With Adverse Event and Adverse Drug Reaction | Number of Participants With Adverse drug Reaction | 5 Participants |
| Cariprazine 6 mg | Number of Participants With Adverse Event and Adverse Drug Reaction | Number of Participants With Adverse event | 9 Participants |
| Cariprazine 6 mg | Number of Participants With Adverse Event and Adverse Drug Reaction | Number of Participants With Adverse drug Reaction | 6 Participants |
| Cariprazine 12.5 mg | Number of Participants With Adverse Event and Adverse Drug Reaction | Number of Participants With Adverse event | 11 Participants |
| Cariprazine 12.5 mg | Number of Participants With Adverse Event and Adverse Drug Reaction | Number of Participants With Adverse drug Reaction | 10 Participants |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14
Time frame: Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14.
Population: Of the 34 participants, 7 subjects who prematurely discontinued during the titration period, 1 subject used prohibited concomitant medication and 1 subject did not take the test product on Day 12 of the fixed-dose period were excluded from the pharmacokinetic analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cariprazine 3 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 135.25 ng*hr/mL | Standard Deviation 64.8 |
| Cariprazine 3 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 298.36 ng*hr/mL | Standard Deviation 128.04 |
| Cariprazine 3 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 1884.24 ng*hr/mL | Standard Deviation 785.73 |
| Cariprazine 6 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 232.38 ng*hr/mL | Standard Deviation 113.31 |
| Cariprazine 6 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 522.38 ng*hr/mL | Standard Deviation 194.61 |
| Cariprazine 6 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 3397.12 ng*hr/mL | Standard Deviation 2395.44 |
| Cariprazine 12.5 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 1017.96 ng*hr/mL | Standard Deviation 419.24 |
| Cariprazine 12.5 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 5950.73 ng*hr/mL | Standard Deviation 1928.05 |
| Cariprazine 12.5 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Last of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 437.64 ng*hr/mL | Standard Deviation 131.76 |
Secondary
Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14
Time frame: Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14.
Population: Of the 34 participants, 7 subjects who prematurely discontinued during the titration period, 1 subject used prohibited concomitant medication and 1 subject did not take the test product on Day 12 of the fixed-dose period were excluded from the pharmacokinetic analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cariprazine 3 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 3.14 ng/mL | Standard Deviation 1.26 |
| Cariprazine 3 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 9.19 ng/mL | Standard Deviation 3.47 |
| Cariprazine 3 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 13.79 ng/mL | Standard Deviation 5.74 |
| Cariprazine 6 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 5.83 ng/mL | Standard Deviation 1.87 |
| Cariprazine 6 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 19.43 ng/mL | Standard Deviation 4.8 |
| Cariprazine 6 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 28.08 ng/mL | Standard Deviation 14.52 |
| Cariprazine 12.5 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 36.39 ng/mL | Standard Deviation 8.53 |
| Cariprazine 12.5 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 54.99 ng/mL | Standard Deviation 14.97 |
| Cariprazine 12.5 mg | Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 11.37 ng/mL | Standard Deviation 3 |
Secondary
Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14
Time frame: Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14.
Population: Of the 34 participants, 7 subjects who prematurely discontinued during the titration period, 1 subject used prohibited concomitant medication and 1 subject did not take the test product on Day 12 of the fixed-dose period were excluded from the pharmacokinetic analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cariprazine 3 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 5.25 hour | Standard Deviation 1.99 |
| Cariprazine 3 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 3.71 hour | Standard Deviation 0.99 |
| Cariprazine 3 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 4.79 hour | Standard Deviation 2.23 |
| Cariprazine 6 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 5.10 hour | Standard Deviation 1.94 |
| Cariprazine 6 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 3.48 hour | Standard Deviation 1.11 |
| Cariprazine 6 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 5.37 hour | Standard Deviation 2.14 |
| Cariprazine 12.5 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | Unchanged MP-214 | 3.22 hour | Standard Deviation 0.45 |
| Cariprazine 12.5 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M6 (didesmethyl cariprazine) | 5.22 hour | Standard Deviation 2.08 |
| Cariprazine 12.5 mg | Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14 | M7 (desmethyl cariprazine) | 4.36 hour | Standard Deviation 1.8 |
Other Pre-specified
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 14 (Last Observation Carried Forward; LOCF)
PANSS score is a 30-item rating scale to assess both the positive and negative symptom syndromes of patients with schizophrenia. Each item is scored on a 7-point scale, from 1 (absent) to 7 (extreme). The PANSS total score of the 30 PANSS items ranges from 30 to 210. High scores indicate greater severity of symptoms.
Time frame: at baseline, and on Day 14 or a last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cariprazine 3 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 14 (Last Observation Carried Forward; LOCF) | -0.2 units on a scale | Standard Deviation 12.8 |
| Cariprazine 6 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 14 (Last Observation Carried Forward; LOCF) | -0.6 units on a scale | Standard Deviation 15.6 |
| Cariprazine 12.5 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 14 (Last Observation Carried Forward; LOCF) | -3.9 units on a scale | Standard Deviation 10.8 |
Other Pre-specified
Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Day 14 (Last Observation Carried Forward; LOCF)
CGI-S is a 7-point scale to assess the global severity of the participant's illness. CGI-S scores range from 1 (normal, not ill at all) to 7 (extremely ill).
Time frame: at baseline, and on Day 14 or a last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cariprazine 3 mg | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Day 14 (Last Observation Carried Forward; LOCF) | 0.3 units on a scale | Standard Deviation 0.8 |
| Cariprazine 6 mg | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Day 14 (Last Observation Carried Forward; LOCF) | -0.1 units on a scale | Standard Deviation 0.9 |
| Cariprazine 12.5 mg | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Day 14 (Last Observation Carried Forward; LOCF) | -0.1 units on a scale | Standard Deviation 0.7 |
Other Pre-specified
The Clinical Global Impression-Improvement (CGI-I) Score at Day 14 (Last Observation Carried Forward; LOCF)
CGI-I is a 7-point scale to assess the global improvement of the participant's illness relative to baseline. CGI-I scores range from 1 (very much improved) to 7 (very much worse).
Time frame: on Day 14 or a last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cariprazine 3 mg | The Clinical Global Impression-Improvement (CGI-I) Score at Day 14 (Last Observation Carried Forward; LOCF) | 4.1 units on a scale | Standard Deviation 1.3 |
| Cariprazine 6 mg | The Clinical Global Impression-Improvement (CGI-I) Score at Day 14 (Last Observation Carried Forward; LOCF) | 3.7 units on a scale | Standard Deviation 1.2 |
| Cariprazine 12.5 mg | The Clinical Global Impression-Improvement (CGI-I) Score at Day 14 (Last Observation Carried Forward; LOCF) | 3.8 units on a scale | Standard Deviation 1.1 |