A Phase 1b, Open-label, Multiple-dose, Randomized, Parallel-arm, Safety, Tolerability, and Pharmacokinetic Trial of Aripiprazole Intramuscular Depot Administered in the Gluteal Muscle in Adult Subjects With Schizophrenia or Bipolar I Disorder

Visual Analog Scale (VAS) Scores for Pain Perception of Aripiprazole 2M LAI 960 mg

时间窗: Day 1 (First injection) to Day 169 (Last injection)

Injection-site pain was evaluated by mean VAS scores as reported by the participant after each injection at visits where an injection occurred. The last injection was the final injection for any given participant. Ratings ranged from 0 (no pain) to 100 (unbearably painful).

VAS Scores for Pain Perception of Aripiprazole IM Depot 400 mg

时间窗: Day 1 (First injection) to Day 197 (Last injection)

Injection-site pain was evaluated by mean VAS scores as reported by the participant after each injection at visits where an injection occurred. The last injection was the final injection for any given participant. Ratings ranged from 0 (no pain) to 100 (unbearably painful).

Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)

时间窗: From first dose of study drug up to 56 days (2M LAI 960 mg) or 28 days (IM depot 400 mg) post last dose of study drug (up to approximately 11 months)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that started after investigational medicinal product (IMP) treatment; or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption, or reduction of the IMP.

Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Score

时间窗: Baseline, Week 32

The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7), dyskinesias (items 8 through 10). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, aware/severe distress). AIMS movement score is the sum of the ratings for the first seven items with the possible total scores of 0 to 28. Negative change from baseline indicates less symptoms.

Number of Participants With Suicidality as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

时间窗: Baseline to Day 225

C-SSRS was used to assess the suicidality of participants during the study. The assessment included "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings were provided for suicidal ideation: Score range of 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent), higher total scores indicate more suicidal ideation; Suicidal behavior: Score range of 0 (no suicidal behavior) to 4 (actual suicide attempt), higher total scores indicate more suicidal behavior. Suicidality was defined as reporting any suicidal ideation or behavior.

Area Under the Plasma Concentration-Time Curve From Time 0 to 56 Days (AUC0-56) of Aripiprazole After the Fourth Dose of Aripiprazole 2M LAI 960 mg

时间窗: Days 169 (predose and 4, 8, 12 hours post dose), 170, 171, 173, 176, 178, 181, 183, 186, 190, 197, 204, 211, 218, and 225

Number of Participants With Potentially Clinically Relevant Clinical Laboratory Abnormalities

时间窗: From first dose of study drug up to Day 225

Potentially clinically relevant laboratory abnormalities included: In units per liter \[U/L\] (alanine aminotransferase: male\[M\]/female\[F\] \>=3 x upper limit of normal (ULN); aspartate aminotransferase: M/F \>= 3 x ULN; creatine kinase: M/F \>= 3 x ULN); in milligrams per deciliter (mg/dL) (creatinine: M/F \>= 2.0; glucose: M/F \>= 200; urate: M \>=10.5, F \>=8.5); potassium \[milliequivalents per liter (mEq/L)\]: M/F \>=5.5, in percentage (%) (eosinophils/leukocytes: M/F\>=10%, hematocrit: M\<=37%/F\<=32% and 3 point decrease from baseline); hemoglobin (grams per deciliter \[g/dL\]): M\<=11.5/F\<=9.5; leukocytes \[10\^9 per liter (/L)\]: M/F\<=2.8 x 10\^3 per microliters (/uL); platelets (10\^9/L): M/F\>=700 x 10\^3/uL; glucose, urine and protein, urine: increase of \>=2 units; and prolactin (nanograms per milliliter \[ng/mL\]: M/F \> 1 x ULN.

Mean Change From Baseline in Simpson-Angus Neurologic Rating Scale (SAS) Total Score

时间窗: Baseline, Week 32

The SAS scale is used to evaluate extrapyramidal symptoms (EPS) and consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Each item is rated on a 5-point scale, with a score of range of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores for all 10 items, possible total score is 0 to 40. Negative change from baseline indicates less symptoms.

Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating After Aripiprazole 2M LAI 960 mg Injection

时间窗: Day 1 (First injection) to Day 169 (Last injection)

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 instrument. Ratings included were: 0 = absent, 1 = mild, 2 = moderate, 3 = severe. The last injection was the final injection for any given participant.

Plasma Concentration of Aripiprazole 56 Days Postdose (C56) of Aripiprazole 2M LAI 960 mg After the Fourth Dose

时间窗: Day 225

Number of Participants With Potentially Clinically Relevant Vital Signs Abnormalities

时间窗: From first dose of study drug up to Day 225

Potentially clinically significant vital sign abnormalities included: heart rate supine (high: \>120 beats per minute \[BPM\] and increase \>=15 BPM; low: \<50 BPM and decrease \>=15 BPM), systolic blood pressure supine (high \>180 (millimetres of mercury \[mmHg\] and increase \>=20 mmHg); low: \<90 mmHg and decrease \>=20 mmHg), diastolic blood pressure supine (high: \>105 mmHg and increase \>=15 mmHg; low: \<50 mmHg and decrease \>=15 mmHg), heart rate standing (high: \>120 BPM and increase \>=15 BPM), systolic blood pressure standing (high: \>180 mmHg and increase \>= 20 mmHg; low: \<90 mmHg and decrease \>=20 mmHg), diastolic blood pressure standing (high: \>105 mmHg and increase \>=15 mmHg), weight in kilograms (kg) (high: increase \>=7%; low: decrease \>=7%), temperature (high: \>=37.8 degree celsius \[°C\] and increase \>=1.1°C), orthostatic hypotension (low: \>=20 mmHg decrease in systolic blood pressure and \>=25 BPM increase in heart rate from supine to standing.

Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities

时间窗: From first dose of study drug up to Day 225

Potentially clinically significant ECG abnormalities included rate: bradycardia (vent \<=50 BPM\] and decrease \>=15 BPM); rhythm: sinus bradycardia (\<= 50 BPM and decrease \>= 15 BPM and no current diagnosis of atrial fibrillation, atrial flutter, or other rhythm abnormality); supraventricular premature beat (not present at baseline and present post baseline); ventricular premature beat (not present at baseline and present post baseline); conduction: right bundle branch block (not present at baseline and present post baseline); ST/T morphology: myocardial ischemia and symmetrical T-wave inversion (not present at baseline and present post baseline), QTcB, QTcF, and QTcN (\>=450 milliseconds \[msec\] and \>= 10% increase).

Mean Change From Baseline in Barnes Akathisia Rating Score (BARS) Global Score

时间窗: Baseline, Week 32

The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation is made on a 6-point scale, with 0 representing absence of symptoms and a score of 5 representing severe akathisia. Total BARS score ranges from 0 to 14 where lower scores indicate less symptoms and negative change from baseline indicate less symptoms.

Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating After Aripiprazole IM Depot 400 mg Injection

时间窗: Day 1 (First injection) to Day 197 (Last injection)

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 instrument. Ratings included were: 0 = absent, 1 = mild, 2 = moderate, 3 = severe. The last injection was the final injection for any given participant.

Plasma Concentration of Aripiprazole 28 Days Postdose (C28) of Aripiprazole IM Depot 400 mg After the Eighth Dose

时间窗: Day 225

Area Under the Plasma Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) of Aripiprazole After the Seventh and Eighth Doses of Aripiprazole IM Depot 400 mg

时间窗: Days 169 (predose and 4, 8, 12 hours post dose), 170, 171, 173, 176, 178, 181, 183, 186, 190, 197 (predose and 4, 8, 12 hours post dose), 198, 199, 201, 204, 206, 209, 211, 214, 218, 225