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SchizophreniaPhase 1NCT01870999

A Multiple Dose Safety, Tolerability and Pharmacokinetics Study in Adult Patients With Schizophrenia Following Administration of Aripiprazole IM Depot

A Phase 1 study testing aripiprazole IM depot and aripiprazole tablets in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate the safety, tolerability, efficacy and pharmacokinetics of aripiprazole intramuscular (IM) depot multiple doses every 4 weeks in adult patients with schizophrenia. Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Schizophrenia
What is being tested?
aripiprazole IM depot and aripiprazole tablets
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
7 sitesUnited States
Study dates
Nov 2007to Oct 2008
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria
  • good physical health as determined by normal medical history, clinical laboratory results, electrocardiograms (ECGs) and physical examinations
  • ability to provide informed consent and/or consent from a legally acceptable representation
  • body mass index (BMI) of 18 to 35 kg/m^2

Who cannot join

  • sexually active males and females of child-bearing potential who are not practicing double barrier birth control or are not abstinent during the study plus 30 days for female or 90 days for males following the last dose of medication
  • history of drug or alcohol abuse within 6 months and/or positive urine drug screen
  • participants who consume alcohol beverages routinely
  • participants who consume alcohol beverages during the screening period
  • use of any antipsychotic medication, other prohibited psychotropic medication, and any cytochrome P450 2D6 (CYP2D6) and cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 inducers within 14 days
  • use of any prescription medication unless approved by Medical Monitor or Study Director
Show all 19Show fewer
  • history of current hepatitis or carrier of HBsAg (Hepatitis B surface antigen) and/or Hepatitis C Virus antibodies (anti-HCV)
  • females who are pregnant or lactating
  • participants who have participated in any clinical trial involving a psychotropic medication within one month prior to enrollment; participants who have participated in a previous IM Depot study within the last 1 year; patients who have previously enrolled and received study medication in an aripiprazole IM Depot clinical trial
  • donation of blood or plasma to a blood bank or in a clinical study (except a screening visit)within 30 days prior to enrollment
  • any major surgery within 30 days prior to enrollment
  • blood transfusion within 30 days prior to enrollment
  • evidence of organ dysfunction or any clinically significant deviation from normal in the physical, electrocardiographic, or clinical laboratory examinations
  • patient represents a significant risk of committing suicide based on history
  • patients currently in an acute relapse
  • patients with Axis I (DSM-IV) diagnosis of schizoaffective or bipolar disorder
  • patients who are considered treatment-resistant to antipsychotic medication
  • patients with a history of neuroleptic malignant syndrome
  • any other sound medical reason as determined by the clinical investigator

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites
  • Otsuka Investigative Site

    Austin, Texas, 78756

  • Otsuka Investigative Site

    Cerritos, California, 90703

  • Otsuka Investigative Site

    Garden Grove, California, 92845

  • Otsuka Investigative Site

    Glendale, California, 91206

  • Otsuka Investigative Site

    Paramount, California, 90723

  • Otsuka Investigative Site

    St Louis, Missouri, 63118

  • Otsuka Investigative Site

    Willingboro, New Jersey, 08046

Other trials in United States

About this study

Official title: An Open-label Parallel Arm Multiple Dose Tolerability, Pharmacokinetics and Safety Study in Adult Patients With Schizophrenia Following Administration of Aripiprazole IM Depot Formulation Once Every Four Weeks

This study will evaluate the safety, tolerability, efficacy and pharmacokinetics of aripiprazole intramuscular (IM) depot multiple doses every 4 weeks in adult patients with schizophrenia.

Conditions
Schizophrenia
Being tested
aripiprazole IM depot, aripiprazole tablets
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • aripiprazole IM depotDrug

    Aripiprazole IM depot supplied as 200 mg or 400 mg vials of lyophilized aripiprazole powder to prepare for IM injection.

  • aripiprazole tabletsDrug

    Aripiprazole tablets 10 mg once daily in the morning for 14 days.

Study groups in NCT01870999
Study groupRoleWhat they receive
400 mg Aripiprazole IM DepotExperimental400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
Receives: Drug: aripiprazole IM depot; Drug: aripiprazole tablets
300 mg Aripiprazole IM DepotExperimental300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
Receives: Drug: aripiprazole IM depot; Drug: aripiprazole tablets
200 mg Aripiprazole IM depotExperimental200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
Receives: Drug: aripiprazole IM depot; Drug: aripiprazole tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events as a Measure of Safety

    Safety and tolerability was assessed by the number of participants with adverse events (AE). An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a subject while enrolled in the study, whether or not it was considered drug-related by the investigator. Abnormal laboratory test findings were considered AEs if, in the opinion of the investigator, they represented an abnormal (ie, clinically significant) change from baseline for that individual participant.

    Measured: 7 Months

  2. Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  3. Aripiprazole Minimum Steady State Plasma Concentration (Css,Min)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,min were determined directly from the observed data at 672 hours after the fifth monthly injection.

    Measured: 672 hours post-dose at Month 5

  4. Aripiprazole Area Under the Concentration-time Curve at Steady-state (AUCτ)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

Secondary outcomes (13)
  1. Aripiprazole Maximum (Peak) Plasma Concentration (Tmax)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for tmax were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  2. Aripiprazole Steady-state Plasma Concentration (Css,Avg)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,avg were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  3. Aripiprazole Terminal-phase Elimination Half-life (t1/2,z)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for t1/2,z were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  4. Dehydro-aripiprazole Maximum Steady State Plasma Concentration (Css,Max)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  5. Dehydro-aripiprazole Minimum Steady State Plasma Concentration (Css,Min)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values for Css,min were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  6. Dehydro-aripiprazole Area Under the Concentration-Time Curve at Steady-State (AUCτ)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  7. Dehydro-aripiprazole Maximum (Peak) Plasma Concentration (Tmax)

    Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values for tmax were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

    Measured: Pre-dose and 1 to 1344 hours post-dose at Month 5

  8. Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 and Week 24

    The PANSS consisted of 3 subscales with a total of 30 symptom constructs each rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The Positive Subscale consisted of 7 positive symptom constructs with a possible subscale score of 7 to 49, the Negative Subscale consisted of 7 negative symptom constructs with a possible subscale score of 7 to 49 and the General Psychopathology Subscale consisted of 16 symptom constructs for a possible subscale score of 16 to 112. The PANSS Total Score ranged from 30 (best) to 210 (worst; indicating more severe symptoms). A Negative change from Baseline indicated improvement.

    Measured: Baseline, Week 12, Week 24

  9. Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Positive Subscale Scores at Week 12 and Week 24

    The PANSS Positive Subscale consisted of 7 symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Severity was rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The total score on the Positive Subscale ranged from 7 to 49 with a higher score indicating more severe symptoms. A Negative change from Baseline indicated improvement.

    Measured: Baseline, Week 12, Week 24

  10. Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Subscale Scores at Week 12 and Week 24

    The PANSS Negative Subscale consisted of 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. Severity was rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The total score on the Negative Subscale ranged from 7 to 49 with a higher score indicating more severe symptoms. A negative change from Baseline indicated improvement.

    Measured: Baseline, Week 12, Week 24

  11. Change From Baseline in the Clinical Global Impression- Severity of Illness Score (CGI-S) at Week 12 and Week 24

    The severity of illness for each participant was rated using the CGI-S scale. The investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" using an 8-point scale where 0=not assessed to 7=among the most extremely ill patients. A negative change from Baseline indicated improvement.

    Measured: Baseline, Week 12, Week 24

  12. Clinical Global Impression-Improvement Scale (CGI-I) at Week 12 and Week 24

    The participant's overall improvement was rated for each participant using the CGI-I scale. The investigator rated the participant's total improvement by answering the following question: "Compared to his/her condition at baseline (prior to randomization), how much has the patient changed?" using an 8-point scale where 0=not assessed, 1=very much improved to 7=very much worse. Lower scores indicated improvement.

    Measured: Baseline, Week 12, Week 24

  13. Number of Participants Hospitalized for Adverse Event "Worsening Schizophrenia"

    The number of participants hospitalized for the Adverse Event "Worsening Schizophrenia included all participants who were hospitalized for any Adverse Event pertaining to the exacerbation of schizophrenic symptoms.

    Measured: 7 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2013 (estimated)
  2. Study startNov 2007
  3. Primary completionOct 2008
  4. Study completionOct 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01870999
Sponsor's protocol ID
31-05-244
Status last verified
Dec 2013
First submitted
4 Jun 2013
Last updated
22 Jan 2014
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing aripiprazole IM depot and aripiprazole tablets in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events as a Measure of Safety (time frame: 7 Months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2014.

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