Body mass index and metabolic parameters in patients with schizophrenia during long-term treatment with paliperidone palmitate

Jennifer Kern Sliwa, Dong-Jing Fu, Cynthia A Bossie, Ibrahim Turkoz, Larry Alphs, Jennifer Kern Sliwa, Dong-Jing Fu, Cynthia A Bossie, Ibrahim Turkoz, Larry Alphs

Abstract

Background: There is a strong association between weight gain and metabolic events in patients with schizophrenia receiving many of the second-generation antipsychotic agents. We explored the relationship between body mass index (BMI) and metabolic events in patients with schizophrenia receiving long-acting injectable paliperidone palmitate (PP) in a long-term trial.

Methods: We conducted a post hoc analysis of data from a PP study that included a 33-week open-label transition (TR) and maintenance phase; a variable duration, randomized, double-blind (DB), placebo-controlled phase and a 52-week open-label extension (OLE) phase. Overall, 644 patients received PP continuously from study entry through discontinuation or study completion and were grouped by baseline BMI (kg/m2): underweight (BMI <19; n = 29, 4.5%), normal-weight (BMI 19- < 25; n = 229, 35.6%), overweight (BMI 25- < 30; n = 232, 36.0%) and obese (BMI ≥ 30; n = 154, 23.9%). Metabolic treatment-emergent adverse events (TEAEs) and changes in related laboratory results from TR baseline were analyzed.

Results: PP exposure was similar across BMI groups; overall mean (SD) dose/month was 70.3 (17.17) mg eq. [109.6 (26.78) mg]; median duration of exposure was 204 days (6 to 1009 days). Occurrences of metabolic TEAEs overall by group were 0% (underweight), 14.9% (normal-weight), 14.7% (overweight), and 24.0% (obese). The most common (≥ 2%) metabolic TEAE were weight gain and elevated blood levels of glucose, lipids, and insulin. Mean BMI and weight increased in normal-weight and overweight groups at DB endpoint, and in underweight, normal-weight and overweight groups at OLE endpoint (p ≤ 0.05). No consistent trend for increased metabolic-related laboratory values by baseline BMI group was observed. Homeostatic model assessments for insulin resistance indicated preexisting insulin resistance at baseline, with minimal changes at OLE endpoint across baseline BMI groups.

Conclusion: Occurrences of metabolic-related TEAEs trended with greater BMI status in patients with schizophrenia treated with PP; consistent trends in metabolic-related laboratory values were not observed.

Trial registration: This study is registered at ClinicalTrials.gov (NCT 00518323).

Trial registration: ClinicalTrials.gov NCT00518323.

Figures

Figure 1
Figure 1
Patient disposition. DB- double-blind; OLE- open-label extension; TR-MA- transition and maintenance.
Figure 2
Figure 2
Treatment-emergent adverse events in ≥5% of patients in any BMI-based group from TR baseline to OLE endpoint. ○ Underweight <19 kg/m2 (n = 29) ∆ Normal-weight 19- < 25 kg/m2 (n = 229) □ Overweight 25- < 30 ◊ kg/m2 (n = 232) Obese ≥30 kg/m2 (n = 154) ● Overall (n = 644). BMI- body mass index; TR- transition; OLE- open-label extension.
Figure 3
Figure 3
Metabolic-related adverse events from TR baseline to OLE endpoint. ○ Underweight <19 kg/m2 (n = 29) ∆ Normal-weight 19- < 25 kg/m2 (n = 229) □ Overweight 25-◊ <30 kg/m2 (n = 232) Obese ≥30 kg/m2 (n = 154) ● Overall (n = 644). OLE- open-label extension; TR-transition.
Figure 4
Figure 4
Mean (SD) weight at TR baseline, DB endpoint and OLE endpoint (ITT analysis set). *p ≤ 0.05; p values are based on change from TR baseline scores and calculated using paired t-test. Baseline values are for those patients for whom both TR baseline and DB (or OLE) endpoint data were available. DB- double-blind; OLE- open-label extension; TR transition; SD- standard deviation.
Figure 5
Figure 5
Mean (SD) BMI at TR baseline, DB endpoint and OLE endpoint (ITT analysis set). *p ≤ 0.05; p values are based on change from TR baseline scores and calculated using paired t-test. Baseline values are for those patients for whom both TR baseline and DB (or OLE) endpoint data were available. DB- double-blind; OLE- open-label extension; TR- transition; SD- standard deviation.

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