Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study

Abstract

Background: A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication.

Methods: Adults were randomly assigned to AL 1064 mg q8wk or PP 156 mg q4wk as inpatients, discharged after 2 weeks, and followed through week 25. Exploratory efficacy measures included the 3 original PANSS subscales, Clinical Global Impression-Severity (CGI-S) subscale, and caregiver Burden Assessment Scale. Exploratory patient-reported outcomes (PROs) included the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) and the Medication Satisfaction Questionnaire. Within-group changes from baseline through week 25 were analyzed for AL and PP separately. PROs were summarized based on observed data.

Results: Of 200 patients randomized (AL, n = 99; PP, n = 101), 99 completed the study (AL, n = 56; PP, n = 43). For AL, PANSS subscale and CGI-S scores improved from baseline through week 25 (mean [SE] change from baseline at week 25: Positive, -7.5 [0.70]; Negative, -3.9 [0.46]; General, -11.8 [0.83]; CGI-S, -1.3 [0.12]). Caregiver burden also improved (mean [SD] changes from baseline at week 9: -8.4 [10.15]; week 25: -8.9 [12.36]). Most AL patients were somewhat/very satisfied with treatment at each timepoint (70.8%-74.7%); mean Q-LES-Q-SF total scores were stable in the outpatient period. For PP, results were similar: PANSS Positive, -7.3 (0.67); Negative, -3.6 (0.69); General, -10.9 (1.22); CGI-S, -1.4 (0.16); caregiver burden, week 9: -8.8 (11.89) and week 25: -9.2 (14.55); satisfaction with treatment, 64.7%-69.3%; and stable Q-LES-Q-SF scores.

Conclusions: ALPINE patients initiating the 2-month AL formulation using the 1-day initiation regimen as inpatients and continuing outpatient care experienced schizophrenia symptom improvement, sustained patient satisfaction with medication, stable quality of life, and reduced caregiver burden. A similar benefit pattern was observed for PP. These results support the feasibility of starting either long-acting injectable in the hospital and transitioning to outpatient treatment.

Trial registration: ClinicalTrials.gov identifier: NCT03345979 [trial registration date: 15/11/2017].

Keywords: Antipsychotic drugs; Dependency burden; Intramuscular injections; Paliperidone palmitate; Quality of life.

Conflict of interest statement

HAN is a consultant or on advisory boards for Acadia, Alkermes, Inc., Allergan, Indivior, Intra-Cellular, Neurocrine, Sunovion, and Teva; and is on the speakers’ bureaus for Acadia, Alkermes, Inc., Allergan, Indivior, Intracellular, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Sunovion, and Teva.

DPW reports receiving research support from Novartis, J&J PRD, Sunovion, Janssen, Alkermes, Inc., Allergan, Takeda, Otsuka, Noven, CoMentis, Intra-Cellular, Lupin, Avanir, Lundbeck, Roche, Boehringer Ingelheim, Acadia, and Sage; and has consulting arrangements with Otsuka and Janssen.

YD, SY, and AC are employees of Alkermes, Inc., and may own stock/options in the company.

PJW and BY were employees of Alkermes, Inc., at the time of the analysis and may own stock/options in the company.

© 2021. The Author(s).

Figures

Fig. 1

ALPINE Study Design and Exploratory Outcome Schedule. aCaregiver-reported outcome; the baseline assessment for the Burden Assessment Scale was completed during the screening period. bPatient-reported outcome. CGI-S, Clinical Global Impression-Severity; IM, intramuscular; PANSS, Positive and Negative Syndrome Scale; Q-LES-Q-SF, Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form

Fig. 2

Change From Baseline in PANSS Subscale and CGI-S Scores With Aripiprazole Lauroxil, Observed Cases. A. PANSS Positive Subscalea. B. PANSS Negative Subscalec. C. PANSS General Psychopathology Subscaled. D. CGI-Sa. PANSS Positive subscale score calculated as sum of items P1–7 (Delusions, Conceptual disorganization, Hallucinatory behavior, Excitement, Grandiosity, Suspiciousness, Hostility); scoring range, 7–49b. Mean baseline score is indicated at the first timepoint; mean (SE) change from baseline scores are indicated at each subsequent timepointc. PANSS Negative subscale score calculated as sum of items N1–7 (Blunted affect, Emotional withdrawal, Poor rapport, Passive-apathetic social withdrawal, Difficulty in abstract thinking, Lack of spontaneity & flow of conversation, Stereotyped thinking); scoring range, 7–49d. PANSS General Psychopathology subscale score calculated as sum of items G1–16 (Somatic concern, Anxiety, Guilt feelings, Tension, Mannerisms & posturing, Depression, Motor retardation, Uncooperativeness, Unusual thought content, Disorientation, Poor attention, Lack of judgment & insight, Disturbance of volition, Poor impulse control, Preoccupation, Active social avoidance); scoring range, 16–112. BL, baseline; CGI-S, Clinical Global Impression−Severity; PANSS, Positive and Negative Syndrome Scale

Fig. 3

Medication Satisfaction Questionnaire Satisfaction with Current Injectable Medication Itema, Aripiprazole Lauroxil Groupa. Patients were asked, “How satisfied are you with your current injectable medication?” Possible responses were very dissatisfied, somewhat dissatisfied, neither, somewhat satisfied, or very satisfied

Fig. 4

Shifts in Satisfaction with Current Injectable Medication, Aripiprazole Lauroxil Group. Gold bars represent patients who were satisfied or very satisfied with their current injectable medication at a given assessment; blue bars indicate patients who were neither satisfied nor dissatisfied, and red bars indicate patients who were dissatisfied or very dissatisfied. Path color indicates patients’ level of satisfaction at the previous MSQ assessment. The width of each bar and path is proportional to the number of patients represented. For example, 5 patients who were satisfied or very satisfied with treatment at week 5 reported that they were dissatisfied or very dissatisfied with treatment at week 9; of those 5, 4 were again satisfied or very satisfied at week 17 while one was neither satisfied nor dissatisfied. All 5 patients who were dissatisfied or very dissatisfied with treatment at week 5 were satisfied or very satisfied at week 9. AL patients who completed MSQ at all 4 timepoints are included; n = 57

Fig. 5

Change From Baseline in PANSS Subscale and CGI-S Scores With Paliperidone Palmitate, Observed Cases. A. PANSS Positive Subscalea.  B. PANSS Negative Subscalec. C. PANSS General Psychopathology Subscaled. D. CGI-Sa. PANSS Positive subscale score calculated as sum of items P1–7 (Delusions, Conceptual disorganization, Hallucinatory behavior, Excitement, Grandiosity, Suspiciousness, Hostility); scoring range, 7–49b. Mean baseline score is indicated at the first timepoint; mean (SE) change from baseline scores are indicated at each subsequent timepointc. PANSS Negative subscale score calculated as sum of items N1–7 (Blunted affect, Emotional withdrawal, Poor rapport, Passive-apathetic social withdrawal, Difficulty in abstract thinking, Lack of spontaneity & flow of conversation, Stereotyped thinking); scoring range, 7–49d. PANSS General Psychopathology subscale score calculated as sum of items G1–16 (Somatic concern, Anxiety, Guilt feelings, Tension, Mannerisms & posturing, Depression, Motor retardation, Uncooperativeness, Unusual thought content, Disorientation, Poor attention, Lack of judgment & insight. Disturbance of volition, Poor impulse control, Preoccupation, Active social avoidance); scoring range, 16–112. BL, baseline; CGI-S, Clinical Global Impression−Severity; PANSS, Positive and Negative Syndrome Scale.

Fig. 6

Medication Satisfaction Questionnairea Satisfaction with Current Injectable Medication Item, Paliperidone Palmitate Group. aPatients were asked, “How satisfied are you with your current injectable medication?” Possible responses were very dissatisfied, somewhat dissatisfied, neither, somewhat satisfied, or very satisfied

Fig. 7

Change in Satisfaction with Current Injectable Medication, Paliperidone Palmitate Group. Gold bars represent patients who were satisfied or very satisfied with their current injectable medication at a given assessment; blue bars indicate patients who were neither satisfied nor dissatisfied, and red bars indicate patients who were dissatisfied or very dissatisfied. Path color indicates patients’ level of satisfaction at the previous MSQ assessment. The width of each bar and path is proportional to the number of patients represented. PP patients who completed MSQ at all 4 timepoints are included; n = 43