Open-label Study to Evaluate the Effectiveness of an Intramuscular Formulation of Aripiprazole (OPC-14597) as Maintenance Treatment in Patients With Bipolar I Disorder

NCT01710709 | Completed Phase 3 Results DMC

• 1 other identifier: 31-08-252
• Study Type: interventional
• Target: 748
• Locations: 10 countries
• Sites: 142

Brief Summary

This will be an open-label uncontrolled trial to evaluate the safety and tolerability of aripiprazole IM depot administered every 4 weeks for up to 52 weeks to patients with bipolar I disorder. The trial will enroll subjects who completed Trial 31-08-250 and de novo subjects not participating in Trial 31-08-250.

Conditions

Bipolar I

Keywords

Aripiprazole, Intramuscular (IM) Depot, Bipolar

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Adverse Events

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or participant enrolled in the clinical trial and which does not necessarily have to have a causal relationship with the investigational medicinal product (IMP). AEs were assessed as a criteria for safety and tolerability.

  Up to Week 52

• Injection Site Pain Measured by the Visual Analog Scale (VAS)

  Injection-site pain was evaluated by mean visual analog scale (VAS) scores as reported by the participant after each injection at visits where an injection occurred. Ratings ranged from 0 (no pain) to 100 (unbearably painful).

  Up to Week 52

• Number of Participants With Clinically Significant Abnormal Laboratory Test Results

  Standard safety variables to be analyzed included clinical laboratory tests. Incidence of treatment emergent adverse events (TEAEs) of potential clinical relevance included abnormal values in serum chemistry, hematology, urinalysis, and other laboratory test that were identified based on pre-defined criteria. Abnormal laboratory values in participants were reported as serious adverse event/adverse events (SAE/AEs) and are reported in the SAE/other AE section of this report.

  Up to Week 52

• Number of Participants With Clinically Significant Abnormal Vital Signs

  TEAEs of potential clinical relevance included abnormal values in body weight, systolic and diastolic blood pressure, heart rate, and body temperature that were identified based on pre-defined criteria. Abnormal laboratory values in participants were reported as SAE/AEs and are reported in the SAE/other AE section of this report.

  Up to Week 52

• Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECGs)

  Twelve-lead ECGs were recorded at specified visits. For each time point, three 12-lead ECG recordings were obtained approximately 5 minutes apart. Additional 12-lead ECGs were permitted to be obtained at the investigator's discretion and were to always be obtained in the event of an early termination. The ECGs were evaluated at the investigational site to determine the participant's eligibility and to monitor safety during the trial.

  Up to Week 52

• Extrapyramidal Symptoms Will be Assessed by Mean Change From Baseline on Abnormal Involuntary Movement Scale(AIMS), Simpson-Angus Scale (SAS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS Only Used in Japan) and Barnes Akathisia Rating Scale (BARS)

  AIMS: 10 items described dyskinesia signs; 0-absence/no awareness; 4-severe condition/severe distress. Total score for Items 1-10 ranges from 0 to 40; a higher score reflects severe condition. SAS:Consisted of 10 parkinsonism signs;1-no symptoms;5-severe.Total score for Items 1-10 ranges from 1 to 50;a higher score reflects severe condition.DIEPSS:A 9-item rating scale (8 assessed individual symptoms \[4 categories of parkinsonism, akathisia, dystonia \& dyskinesia\]+1 assessed general severity) was used;0-no symptoms/normal, 4-severe.Total score (8 individual symptom items) was in range of 0 to 32 (a higher score reflects severe condition).BARS:Consisted of 4 items related to akathisia:objective observation, subjective feelings of restlessness, distress, global clinical evaluation.Only BARS global clinical assessment score has been presented and rated using scale:0-absence of symptoms;5-severe akathisia.Total BARS global score ranges from 0 to 5,a higher score reflects severe condition.

  Baseline, Week 28, and Week 52

• Number of Participants Experiencing Suicidal Events and Their Classification According to the Completion of Columbia Suicide Severity Rating Scale (C-SSRS)

  Suicidality was monitored throughout the trial using the C-SSRS at every visit. The C-SSRS scale consisted of a screening/baseline evaluation that assessed the participant's lifetime experience and experience over the last 90 days with suicide events and suicidal ideation and a post-baseline/ "Since Last Visit" evaluation that focused on suicidality since the last trial visit.

  Up to Week 52

• Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating

  Injection-site reactions were assessed by the investigator (or qualified designee) and the participant. Investigators rated localized pain, redness, swelling, and induration at the most recent injection site using a 4-point categorical scale (absent, mild, moderate, severe) . The participant indicated the degree of pain at the most recent injection site using a VAS. Ratings ranged from 0 (no pain) to 100 (unbearably painful). Ratings included were: 0 = absent, 1 = mild, 2 = moderate, 3 = severe. These assessments occurred at trial visits where injections occurred (scheduled and unscheduled), beginning with the first dose of open-label aripiprazole IM depot administered at the final visit of the Oral Stabilization Phase and continued through the last injection prior to the end of the IM Depot Maintenance Phase/Early termination (ET) visit (ie, evaluations were not done at end of the IM Depot Maintenance Phase/ET visit).

  Up to Week 52

Secondary Outcomes (1)

• Percentage of Participants Who Remained Stable at End of Treatment in Phase C

  Up to Week 52

Study Arms (1)

Experimental

EXPERIMENTAL

Aripiprazole, Intramuscular (IM) Depot

Drug: Aripiprazole

Interventions

Aripiprazole DRUG

400mg or 300mg, intramuscular injections every 4 weeks.

Experimental

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completed participation in Trial 31-08-250
• De novo subjects not participating in Trial 31-08-250
• Subjects who are able to provide written informed consent.
• Male and female subjects 18 years of age or older at time of informed consent
• Subjects who, in the investigator's judgment, require chronic treatment with an antipsychotic medication for their bipolar I disorder and would benefit from extended treatment with a long-acting injectable formulation
• Subjects who have a recurrence of mood episode or exacerbations of mood symptoms when they are not receiving treatment for their bipolar I disorder or are noncompliant with treatment for their bipolar I disorder
• Have an outpatient status

You may not qualify if:

• Experienced 9 or more mood episodes within the past year
• A current manic episode with a duration of \> 2 years
• Currently meet DSM-IV-TR criteria for substance abuse or substance dependence; this includes the abuse of alcohol and benzodiazepines, but excludes the use of caffeine and/or nicotine
• Hypothyroidism or hyperthyroidism, unless condition has been stabilized
• Diagnosed with epilepsy or a history of seizures
• Known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones
• Sexually active women of childbearing potential and sexually active men who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during this trial and for 180 days following the last dose of trial medication
• Females breastfeeding or pregnant (positive blood pregnancy test prior to receiving trial drug)
• Risk of committing suicide
• Abnormal laboratory test results, vital signs and ECG results
• Participated in any clinical trial other than Trial 250 with an investigational agent within the 30 days prior to screening
• Had electroconvulsive therapy (ECT) treatment during the current episode or within 3 months
• Subjects who have not met criteria for stabilization for 4 consecutive weeks

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (142)

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Birmingham, Alabama, 35226, United States

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Little Rock, Arkansas, 72211, United States

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Rogers, Arkansas, 72758, United States

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Bellflower, California, 90706, United States

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Beverly Hills, California, 90210, United States

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Costa Mesa, California, 92626, United States

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Culver City, California, 90230, United States

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Garden Grove, California, 92845, United States

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Lemon Grove, California, 91945, United States

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Oakland, California, 94607, United States

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Orange, California, 92868, United States

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Pico Rivera, California, 90660, United States

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Riverside, California, 92506, United States

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San Diego, California, 92102, United States

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Temecula, California, 92591, United States

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Upland, California, 91786, United States

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Wildomar, California, 92595, United States

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Colorado Springs, Colorado, 80910, United States

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Gainesville, Florida, 32607, United States

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Hialeah, Florida, 33012, United States

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Jacksonville, Florida, 32256, United States

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Leesburg, Florida, 34748, United States

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Orlando, Florida, 32801, United States

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Tampa, Florida, 33613, United States

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Atlanta, Georgia, 30331, United States

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Decatur, Georgia, 30030, United States

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Smyrna, Georgia, 30080, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60612, United States

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Hinsdale, Illinois, 60522, United States

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Naperville, Illinois, 60563, United States

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Schaumburg, Illinois, 60194, United States

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Prairie Village, Kansas, 66206, United States

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Lake Charles, Louisiana, 70629, United States

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Baltimore, Maryland, 21208, United States

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Gaithersburg, Maryland, 20877, United States

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Boston, Massachusetts, 02131, United States

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O'Fallon, Missouri, 63368, United States

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St Louis, Missouri, 63128, United States

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Lincoln, Nebraska, 68526, United States

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Berlin, New Jersey, 08009, United States

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Cherry Hill, New Jersey, 08002, United States

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Brooklyn, New York, 11241, United States

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Buffalo, New York, 14215, United States

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New York, New York, 10003, United States

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New York, New York, 10023, United States

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Rochester, New York, 14615, United States

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Rochester, New York, 14618, United States

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Staten Island, New York, 10305, United States

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Staten Island, New York, 10312, United States

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Cincinnati, Ohio, 45219, United States

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Oklahoma City, Oklahoma, 73103, United States

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Oklahoma City, Oklahoma, 73112, United States

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Oklahoma City, Oklahoma, 73118, United States

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Portland, Oregon, 97210, United States

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Allentown, Pennsylvania, 18104, United States

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Media, Pennsylvania, 19063, United States

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Columbia, South Carolina, 29201, United States

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Memphis, Tennessee, 38119, United States

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Arlington, Texas, 76012, United States

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Austin, Texas, 78754, United States

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Dallas, Texas, 75243, United States

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Plano, Texas, 75074, United States

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Plano, Texas, 75093, United States

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Sugar Land, Texas, 77478, United States

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Wichita Falls, Texas, 76309, United States

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Orem, Utah, 84058, United States

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Salt Lake City, Utah, 84106, United States

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Richmond, Virginia, 23230, United States

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Bellevue, Washington, 98007, United States

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Spokane, Washington, 99204, United States

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Middleton, Wisconsin, 53562, United States

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Kentville, Nova Scotia, B4N 4K9, Canada

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Chatham, Ontario, N7L 1C1, Canada

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Élancourt, 78990, France

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Limoges, 87025, France

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Nîmes, 30900, France

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Toulouse, 31000, France

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Budapest, H-1135, Hungary

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Nyireghaza, H-4400, Hungary

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Vác, H-2600, Hungary

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Fukuoka, 814-0133, Japan

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Fukuoka, 819-0037, Japan

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Fukuoka, 830-0033, Japan

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Fukushima, 960-0102, Japan

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Fukushima, 961-0021, Japan

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Fukushima, 963-0207, Japan

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Gunma, 375-0017, Japan

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Gunma, 377-0055, Japan

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Ibaraki, 311-3193, Japan

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Ibaraki, 319-1221, Japan

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Iizuka, 820-0014, Japan

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Kanagawa, 216-8511, Japan

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Kanagawa, 221-0801, Japan

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Kanagawa, 223-0062, Japan

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Kanagawa, 225-0003, Japan

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Kanagawa, 238-0042, Japan

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Kanagawa, 259-1304, Japan

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Kochi, 783-8505, Japan

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Kouchi, 780-0062, Japan

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Kumamoto, 861-8002, Japan

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Nagano-ken, 380-8582, Japan

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Okayama, 700-0915, Japan

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Okinawa, 901-1105, Japan

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Okinawa, 901-2553, Japan

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Osaka, 567-0017, Japan

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Ōsaka, 545-8586, Japan

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Ōsaka, 569-1041, Japan

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Ōsaka, 570-0005, Japan

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Ōsaka, 573-1183, Japan

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Ōsaka, 589-0011, Japan

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Sapporo, 002-8029, Japan

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Shizuoka, 420-0839, Japan

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Tokyo, 151-0053, Japan

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Tokyo, 162-0843, Japan

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Tokyo, 170-0002, Japan

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Tokyo, 175-0091, Japan

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Tokyo, 175-0094, Japan

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Tokyo, 187-8551, Japan

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Yamagata, 992-0601, Japan

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Yatsushiro, 866-0043, Japan

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Johor Bahru, 31250, Malaysia

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Perak, 30450, Malaysia

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Sarawak, 93250, Malaysia

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Bydgoszcz, 85-001, Poland

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Chełmno, 86-200, Poland

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Choroszcz, 16-070, Poland

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Gdansk, 80-438, Poland

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Lublin, 20-109, Poland

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Pruszków, 05-802, Poland

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Tuszyn, 95-080, Poland

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Bucharest, 010825, Romania

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Bucharest, 030455, Romania

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Bucharest, 041915, Romania

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Iași, 700282, Romania

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Târgovişte, 130086, Romania

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Târgu Mureş, 540096, Romania

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Goyang-si, 10326, South Korea

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Jeju City, 690-767, South Korea

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Seoul, 136-705, South Korea

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Seoul, 139-711, South Korea

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Taipei, 110, Taiwan

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Related Publications (1)

• Calabrese JR, Jin N, Johnson B, Such P, Baker RA, Madera J, Hertel P, Ottinger J, Amatniek J, Kawasaki H. Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study. Int J Bipolar Disord. 2018 Jun 10;6(1):14. doi: 10.1186/s40345-018-0122-z.

  PMID: 29886522 DERIVED

MeSH Terms

Interventions

Aripiprazole

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

DT-inquiry@otsuka.jp

Study Officials

• Joan Amatniek, MD

  Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2012
• First Posted: October 19, 2012
• Study Start: November 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 21, 2018
• Results First Posted: August 8, 2018

Record last verified: 2018-08

Locations

FR (4); RO (6); CA (2); MY (3); JP (40); TW (1); US (72); HU (3); KR (4); PL (7)