New formulation associated with delayed time to impending relapse, as well as improvements on measures of symptom severity and treatment response.
New York, NY — In a study to evaluate the ability of a once-monthly intramuscular depot formulation of aripiprazole to maintain stability over time in adult patients who meet DSM-IV-TR schizophrenia criteria, aripiprazole IM-depot significantly delayed time to impending relapse as explained in a poster presented at the American Psychiatric Association 64th Institute on Psychiatric Services.
“One of the problems we encounter in patients with schizophrenia is medication adherence. Patients have difficulty remembering to take their pills. This leads to relapse and rehospitalization,” explained Timothy Peters-Strickland, MD, Director of Global Clinical Development for Otsuka. “The use of long-acting injectables can improve adherence.”
The study of 843 enrolled patients was a three-year multicenter trial in 108 centers across the United States and 11 other countries conducted from 2008 to 2011. Study participants were adults ages 18 to 60 who had a diagnosis of schizophrenia as defined by the DSM-IV-TR for at least three years and who had a history of relapse when not on antipsychotic medication. Exclusion criteria were other psychiatric illness, significant medical or neurologic disorder, or abnormal ECG on screening.
The study design included screening and four phases. In phase 1, participants not already taking aripiprazole were titrated from other antipsychotics to oral aripiprazole. Doses of aripiprazole were 5 mg/d in week 1and 10 mg/d in week 2 along with tapered doses of their previous antipsychotic, which was discontinued at weeks 4-6. In phase 2, participants were stabilized on oral aripiprazole, 10-30 mg/d. In phase 3, patients who met stability criteria were assigned to single-blind 400 mg aripipraozle-IM-depot, with oral aripiprazole continued for a two-week transition period. Those who met stability criteria for 12 weeks were randomly assigned (2:1) to aripiprazole IM-depot (n=269) or placebo (n = 134) administered every four weeks. The primary outcome measure was time to worsening of psychotic symptoms with impending relapse.
Results showed that time to impending relapse was significantly delayed for aripipraozle-IM-depot compared with placebo. The aripiprazole-IM-depot group also showed improvements on the Clinical Global Impression - Severity of Illness scale.
“The results were robustly positive. In fact, we terminated the trial early because the interim analysis was positive,” said Peters-Strickland. The trial was stopped once the preplanned interim analysis showed clear clinical efficacy for aripiprazole-IM-depot compared with placebo. Continuing would have kept the control group on placebo rather than providing them with treatment.
“The side-effect profile for aripiprazole-IM-depot is low similar to oral aripiprazole. It is the same composition but a different formulation,” Peters-Strickland explained. “In the study there were no unusual shifts in lab values or fasting metabolic parameters compared to oral aripiprazole or placebo. Adverse events were not different than what we see with the oral formulation. The one variation in the study was an increase of 5% in tremors, which was twice that seen with placebo.”
Aripiprazole is reported to be the first dopamine partial agonist in depot formulation, and has been submitted for FDA approval.