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Safety, Pharmacokinetics and Efficacy Study of MP-214 in Patients With Schizophrenia

Sponsor
Mitsubishi Tanabe Pharma Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT00862992
Collaborator
(none)
34
Enrollment
1
Location
3
Arms
17
Duration (Months)
2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Cariprazine 3 mg
  • Drug: Cariprazine 6 mg
  • Drug: Cariprazine 12.5 mg
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of MP-214 in Patients With Schizophrenia (Exploratory Study)
Study Start Date :
Apr 1, 2008
Actual Primary Completion Date :
Sep 1, 2009
Actual Study Completion Date :
Sep 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Drug: Cariprazine 3 mg
Other Names:
  • Cariprazine(INN)
  • RGH-188

    		•
    Experimental: 2

    Drug: Cariprazine 6 mg
    Experimental: 3

    Drug: Cariprazine 12.5 mg

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Event and Adverse Drug Reaction [Up to 7 weeks]

    Secondary Outcome Measures

    1. 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.]

    2. 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.]

    3. 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 Outcome Measures

    1. 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.

    2. 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).

    3. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hoyu Hospital Kure-City Hiroshima-ken Japan

    Sponsors and Collaborators

    • Mitsubishi Tanabe Pharma Corporation

    Investigators

    • Study Chair: Teruhiko Higuchi, President, National Center of Neurology and Psychiatry

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mitsubishi Tanabe Pharma Corporation
    ClinicalTrials.gov Identifier:
    NCT00862992
    Other Study ID Numbers:
    • A002-A3
    First Posted:
    Mar 17, 2009
    Last Update Posted:
    Apr 12, 2021
    Last Verified:
    Apr 1, 2021
    Keywords provided by Mitsubishi Tanabe Pharma Corporation
    schizophrenia
    antipsychotics
    dopamine D3/D2 antagonist
    Additional relevant MeSH terms:
    Schizophrenia
    Cariprazine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Period Title: Overall Study
    STARTED 12 10 12
    COMPLETED 9 9 9
    NOT COMPLETED 3 1 3

    Baseline Characteristics

    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg Total
    Arm/Group Description Total of all reporting groups
    Overall Participants 12 10 12 34
    Age, Customized (Count of Participants)
    <18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    >=18 and =<30 years
    2
    16.7%
    2
    20%
    2
    16.7%
    6
    17.6%
    >=31 and =<40 years
    2
    16.7%
    4
    40%
    3
    25%
    9
    26.5%
    >=41 and =<55 years
    6
    50%
    3
    30%
    5
    41.7%
    14
    41.2%
    >55 years
    2
    16.7%
    1
    10%
    2
    16.7%
    5
    14.7%
    Sex: Female, Male (Count of Participants)
    Female
    6
    50%
    4
    40%
    4
    33.3%
    14
    41.2%
    Male
    6
    50%
    6
    60%
    8
    66.7%
    20
    58.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Event and Adverse Drug Reaction
    Description
    Time Frame Up to 7 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 12 10 12
    Number of Participants With Adverse event
    9
    75%
    9
    90%
    11
    91.7%
    Number of Participants With Adverse drug Reaction
    5
    41.7%
    6
    60%
    10
    83.3%
    2. Secondary Outcome
    Title Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14
    Description
    Time Frame Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14.

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 9 8 8
    Unchanged MP-214
    9.19
    (3.47)
    19.43
    (4.80)
    36.39
    (8.53)
    M7 (desmethyl cariprazine)
    3.14
    (1.26)
    5.83
    (1.87)
    11.37
    (3.00)
    M6 (didesmethyl cariprazine)
    13.79
    (5.74)
    28.08
    (14.52)
    54.99
    (14.97)
    3. Secondary Outcome
    Title Time to Maximum Plasma Concentration of Unchanged MP-214, M7 (Desmethyl Cariprazine) and M6 (Didesmethyl Cariprazine) at Day 14
    Description
    Time Frame Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14.

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 9 8 8
    Unchanged MP-214
    3.71
    (0.99)
    3.48
    (1.11)
    3.22
    (0.45)
    M7 (desmethyl cariprazine)
    5.25
    (1.99)
    5.10
    (1.94)
    4.36
    (1.80)
    M6 (didesmethyl cariprazine)
    4.79
    (2.23)
    5.37
    (2.14)
    5.22
    (2.08)
    4. Secondary Outcome
    Title 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
    Description
    Time Frame Pre-dose, 3, 4, 6, 8, 24, 48, 72, 96 and 168 hours post-dose of Day 14.

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 9 8 8
    Unchanged MP-214
    298.36
    (128.04)
    522.38
    (194.61)
    1017.96
    (419.24)
    M7 (desmethyl cariprazine)
    135.25
    (64.80)
    232.38
    (113.31)
    437.64
    (131.76)
    M6 (didesmethyl cariprazine)
    1884.24
    (785.73)
    3397.12
    (2395.44)
    5950.73
    (1928.05)
    5. Other Pre-specified Outcome
    Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 14 (Last Observation Carried Forward; LOCF)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 12 10 12
    Mean (Standard Deviation) [units on a scale]
    -0.2
    (12.8)
    -0.6
    (15.6)
    -3.9
    (10.8)
    6. Other Pre-specified Outcome
    Title Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Day 14 (Last Observation Carried Forward; LOCF)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 12 10 12
    Mean (Standard Deviation) [units on a scale]
    0.3
    (0.8)
    -0.1
    (0.9)
    -0.1
    (0.7)
    7. Other Pre-specified Outcome
    Title The Clinical Global Impression-Improvement (CGI-I) Score at Day 14 (Last Observation Carried Forward; LOCF)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    Measure Participants 12 10 12
    Mean (Standard Deviation) [units on a scale]
    4.1
    (1.3)
    3.7
    (1.2)
    3.8
    (1.1)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Arm/Group Description
    All Cause Mortality
    Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/12 (25%) 1/10 (10%) 2/12 (16.7%)
    Injury, poisoning and procedural complications
    Tibia fracture 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Investigations
    Blood creatine phosphokinase increased 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Nervous system disorders
    Neuroleptic malignant syndrome 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Psychiatric disorders
    Schizophrenia 2/12 (16.7%) 1/10 (10%) 1/12 (8.3%)
    Other (Not Including Serious) Adverse Events
    Cariprazine 3 mg Cariprazine 6 mg Cariprazine 12.5 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/12 (75%) 9/10 (90%) 11/12 (91.7%)
    Cardiac disorders
    Sinus bradycardia 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Ear and labyrinth disorders
    Vertigo 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Endocrine disorders
    Hyperthyroidism 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Eye disorders
    Conjunctivitis 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Dry eye 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Gastrointestinal disorders
    Abdominal distension 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Abdominal pain upper 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Cheilitis 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Constipation 0/12 (0%) 1/10 (10%) 1/12 (8.3%)
    Diarrhoea 2/12 (16.7%) 1/10 (10%) 3/12 (25%)
    Enterocolitis 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Gastritis 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Inguinal hernia 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Lip dry 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Nausea 2/12 (16.7%) 1/10 (10%) 0/12 (0%)
    Salivary hypersecretion 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Stomatitis 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Toothache 0/12 (0%) 2/10 (20%) 0/12 (0%)
    General disorders
    Feeling abnormal 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Malaise 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Pyrexia 0/12 (0%) 0/10 (0%) 2/12 (16.7%)
    Thirst 0/12 (0%) 0/10 (0%) 2/12 (16.7%)
    Infections and infestations
    Nasopharyngitis 2/12 (16.7%) 3/10 (30%) 1/12 (8.3%)
    Urinary tract infection 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Injury, poisoning and procedural complications
    Contusion 1/12 (8.3%) 1/10 (10%) 0/12 (0%)
    Hand fracture 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Nail injury 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Skin laceration 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Thermal burn 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Investigations
    Alanine aminotransferase increased 1/12 (8.3%) 0/10 (0%) 3/12 (25%)
    Aspartate aminotransferase increased 1/12 (8.3%) 1/10 (10%) 2/12 (16.7%)
    Blood bilirubin increased 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Blood creatine phosphokinase increased 1/12 (8.3%) 1/10 (10%) 3/12 (25%)
    Blood lactate dehydrogenase increased 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Blood potassium increased 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Blood pressure decreased 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Blood pressure increased 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Blood prolactin increased 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Blood triglycerides increased 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Blood uric acid increased 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Blood urine present 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Glucose urine present 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Hepatic enzyme increased 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    White blood cell count decreased 0/12 (0%) 1/10 (10%) 0/12 (0%)
    White blood cell count increased 0/12 (0%) 0/10 (0%) 3/12 (25%)
    Metabolism and nutrition disorders
    Polydipsia 0/12 (0%) 0/10 (0%) 2/12 (16.7%)
    Musculoskeletal and connective tissue disorders
    Arthritis 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Myalgia 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Nervous system disorders
    Akathisia 1/12 (8.3%) 1/10 (10%) 3/12 (25%)
    Dysarthria 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Headache 1/12 (8.3%) 0/10 (0%) 1/12 (8.3%)
    Hyperaesthesia 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Hypoaesthesia 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Parkinsonism 0/12 (0%) 1/10 (10%) 1/12 (8.3%)
    Sleep paralysis 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Somnolence 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Tremor 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Psychiatric disorders
    Insomnia 4/12 (33.3%) 3/10 (30%) 1/12 (8.3%)
    Restlessness 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Renal and urinary disorders
    Dysuria 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Pollakiuria 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Urinary retention 0/12 (0%) 1/10 (10%) 1/12 (8.3%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Productive cough 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Upper respiratory tract inflammation 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis contact 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Eczema 1/12 (8.3%) 0/10 (0%) 0/12 (0%)
    Hyperkeratosis 0/12 (0%) 0/10 (0%) 1/12 (8.3%)
    Social circumstances
    Poor personal hygiene 0/12 (0%) 1/10 (10%) 0/12 (0%)
    Vascular disorders
    Orthostatic hypotension 1/12 (8.3%) 1/10 (10%) 1/12 (8.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Results Point of Contact

    Name/Title Clinical Trials, Information Desk
    Organization Mitsubishi Tanabe Pharma Corporation
    Phone
    Email cti-inq-ml@ml.mt-pharma.co.jp
    Responsible Party:
    Mitsubishi Tanabe Pharma Corporation
    ClinicalTrials.gov Identifier:
    NCT00862992
    Other Study ID Numbers:
    • A002-A3
    First Posted:
    Mar 17, 2009
    Last Update Posted:
    Apr 12, 2021
    Last Verified:
    Apr 1, 2021