ABILIFY MAINTENA (Page 9 of 11)

14.2 Bipolar I Disorder – Maintenance Monotherapy

The efficacy of ABILIFY MAINTENA for the maintenance treatment of bipolar I disorder was established in a 52-week, double-blind, placebo-controlled, randomized withdrawal trial in adult patients who were experiencing a manic episode at trial entry, met DSM-IV-TR criteria for bipolar I disorder, and had a history of at least one previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent.

Clinical ratings during this trial included:

  • Young Mania Rating Scale (YMRS)-an 11-item, clinician-rated scale used to assess the degree of manic symptomatology, in a range with 0 representing no symptoms, and 60 representing worst symptoms.
  • Montgomery-Asberg Depression Rating Scale (MADRS) – a 10-item clinician-related scale used to assess the degree of depressive symptomatology, with 1 representing no symptoms, and 60 representing worst symptoms.
  • Clinical Global Impression Bipolar Version Severity of Illness (CGI-BP-S) a scale of 1 (normal, not at all ill) to 7 (very severely ill patient) based on the patient’s severity of illness mania, depression, and overall bipolar illness.

This trial included:

  • A 4 to 6 week, open-label, oral conversion phase for patients on treatments for bipolar I disorder other than aripiprazole. A total of 466 patients entered this phase.
  • A 2 to 8 week, open-label, oral aripiprazole stabilization phase (target dose of 15 mg to 30 mg once daily). A total of 632 patients entered this phase. Patients were 18 to 65 years old (mean 40.7 years) and 60% were female. The mean (range) baseline scores were: YMRS total, 16.9 MADRS total, 5.7, and CGI-BP-S overall, 3.4 (mildly to moderately ill). Prior to the next phase, stabilization was required. Stabilization was defined as having all of the following at one bi-weekly visit: Outpatient status, YMRS total score ≤12, MADRS total score ≤12, no active suicidality; with active suicidality defined as a score of 4 or more on the MADRS item 10 OR an answer of “yes” on question 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS).
  • A minimum 12-week, uncontrolled, single-blind ABILIFY MAINTENA stabilization phase (treatment with 400 mg of ABILIFY MAINTENA given every 4 weeks in conjunction with oral aripiprazole [10 mg to 20 mg/day] for the first 2 weeks). The dose of ABILIFY MAINTENA was allowed to be decreased to 300 mg due to adverse reactions. A total of 425 patients entered this phase. The mean (range) baseline scores were: YMRS total, 5.8, MADRS total 3.7, and CGI-BP-S overall, 2.1 (minimally ill). Prior to the next phase, stabilization was required (see above for the definition of stabilization) for 8 consecutive weeks starting at week 6.
  • A double-blind, placebo-controlled, randomized-withdrawal phase to observe for recurrence to a mood episode (defined below) for up to 52 weeks. A total of 266 patients were randomized 1:1 to the same dose of ABILIFY MAINTENA they were receiving at the end of the stabilization phase, (400 mg or 300 mg administered once every 4 weeks) or placebo. The mean (range) baseline scores were: YMRS total, 2.8 (0 to 12), MADRS total, 2.7 (0 to 12), and CGI-S overall, 1.7 (minimally ill). The dose could be decreased to 300 mg for tolerability and returned once to 400 mg.

The primary efficacy endpoint was time from randomization to recurrence of any mood episode. Recurrence was defined as the first occurrence of one or more of the following criteria:

  • Hospitalization for any mood episode OR
  • Any of the following:
    • YMRS total score ≥15 OR
    • MADRS total score ≥15 OR
    • Clinical Global Impression — Bipolar Version-Severity (CGI-BP-S) score >4 (overall score) OR
  • Serious adverse event (SAE) of worsening disease (bipolar I disorder) OR
  • Discontinuation due to lack of efficacy or discontinuation due to an adverse event (AE) of worsening disease OR
  • Clinical worsening with the need for addition of a mood stabilizer, antidepressant treatment, antipsychotic medication, and/or increase greater than the allowed benzodiazepine doses for treatment of symptoms of an underlying mood disorder OR
  • Active suicidality, which is defined as a score of 4 or more on the MADRS item 10 OR an answer of “yes” on question 4 or 5 on the C-SSRS

Analysis demonstrated a statistically significantly longer time to recurrence of any mood episode in subjects randomized to the ABILIFY MAINTENA group than compared to placebo-treated subjects. The Kaplan-Meier curves of the time of recurrence to any mood episode during the double-blind treatment phase for ABILIFY MAINTENA and placebo groups are shown in Figure 26.

*
This figure is based on a total of 103 recurrence events.
Figure 26: Kaplan-Meier Estimation of Cumulative Recurrence Rate for Any Mood Episode *
Figure 26
(click image for full-size original)

Analysis by type of mood recurrence demonstrated a statistically significantly longer time to recurrence for both manic and mixed mood episodes in subjects treated with ABILIFY MAINTENA compared to those treated with placebo. There was no substantial difference between treatment groups in delaying time to recurrence of depressive mood episodes.

An examination of subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, sex, or race.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Pre-filled Dual Chamber Syringe:

ABILIFY MAINTENA (aripiprazole) pre-filled dual chamber syringe for extended-release injectable suspension in single-use syringes is available in 300-mg or 400-mg strength syringes. The pre-filled dual chamber syringe consists of a front chamber that contains the lyophilized powder of aripiprazole monohydrate and a rear chamber that contains sterile water for injection.

The 300-mg kit includes (NDC 59148-045-80):

  • 300-mg single-dose, pre-filled, dual chamber syringe containing ABILIFY MAINTENA (aripiprazole) for extended-release injectable suspension lyophilized powder and Sterile Water for Injection
  • One 23-gauge, 1-inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients
  • One 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients
  • One 21-gauge, 2-inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients

The 400-mg kit includes (NDC 59148-072-80):

  • 400-mg, single-dose, pre-filled, dual chamber syringe containing ABILIFY MAINTENA (aripiprazole) for extended-release injectable suspension lyophilized powder and Sterile Water for Injection
  • One 23-gauge, 1-inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients
  • One 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients
  • One 21-gauge, 2-inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients

Single-Use Vial:

ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension in single-use vials is available in 300-mg or 400-mg strength vials.

The 300-mg kit includes (NDC 59148-018-71):

  • 300-mg, single-use vial of ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension lyophilized powder
  • 5-mL, single-use vial of Sterile Water for Injection, USP
  • One 3-mL, luer lock syringe with pre-attached 21-gauge, 1.5-inch hypodermic safety needle with needle protection device
  • One 3-mL, luer lock disposable syringe with luer lock tip
  • One vial adapter
  • One 23-gauge, 1-inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients
  • One 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients
  • One 21-gauge, 2-inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients

The 400-mg kit includes (NDC 59148-019-71):

  • 400-mg, single-use vial of ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension lyophilized powder
  • 5-mL, single-use vial of Sterile Water for Injection, USP
  • One 3-mL, luer lock syringe with pre-attached 21-gauge, 1.5-inch hypodermic safety needle with needle protection device
  • One 3-mL, luer lock disposable syringe with luer lock tip
  • One vial adapter
  • One 23-gauge, 1-inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients
  • One 22-gauge, 1.5-inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients
  • One 21-gauge, 2-inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.