ECE2020 Audio ePoster Presentations Pituitary and Neuroendocrinology (217 abstracts)
Impact of imputation method on efficacy results from the phase 3 optimal study of oral octreotide capsules in adult patients with acromegaly
Susan Samson 1 , Lisa Nachtigall 2 , Maria Fleseriu 3 , Murray Gordon 4 , Mojca Jensterle 5 , Atanaska Elenkova 6 , Mark E Molitch 7 , William Ludlam 8 , Gary Patou 8 , Asi Haviv 8 , Nienke Biermasz 9 , Peter Trainer 10 , Christian J Strasburger 11 , Laurence Kennedy 12 & Shlomo Melmed 13
1Baylor College of Medicine, Houston, United States; 2MGH Neuroendocrine and Pituitary Center, Chestnut Hill, United States; 3Oregon Health and Science University, Portland, United States; 4Allegheny General Hospital, Pittsburg, United States; 5University Medical Center Ljubljana, Ljubljana, Slovenia; 6Medical University Sofia, USHATE, Sofia, Bulgaria; 7Northwestern University, Evanston, United States; 8Chiasma, Waltham, United States; 9Leiden University Medical Center, Oegstgeest, Netherlands; 10The Christie NHS Foundation Trust, Manchester, United Kingdom; 11Charite Campus Mitte, Berlin, Germany; 12Cleveland Clinic Foundation, Cleveland, United States; 13Cedars Sinai Medical Center, Los Angeles, United States
Objective: The phase 3 CHIASMA OPTIMAL study assessed efficacy and safety of oral octreotide capsules (OOC) in patients with acromegaly controlled on injectable somatostatin receptor ligands (SRLs). Sensitivity analyses were conducted for efficacy endpoints using two methods of imputation (i.e., the process of replacing clinical data with substitution values) to address missing data points due to some subjects reverting back to their prior injectable SRL treatment.
Methods: Patients were ≥ 18 years of age and had evidence of active acromegaly with an average IGF-I ≤ 1.0 × ULN (utilizing the IDS iSYS assay calibrated to WHO recombinant reference standard 02/254). At baseline, patients were randomized to receive OOC or placebo for 36 weeks. The primary endpoint wasproportion of patients maintaining biochemical response, defined as IGF-I ≤ 1.0 × ULN (2-value average at weeks 34 and 36) (Samson et al. ENDO 2020). Per study protocol, patient study discontinuations were considered non-responders regardless of clinical response at the time of discontinuation (non-response imputation). Additional exploratory analyses were performed utilizing the last observation carried forward (LOCF) analysis, as well as a completers analysis of response among the subgroup that completed the entire 36 weeks on study drug. The response rates reported for the primary end point are slightly adjusted for stratification differences as prespecified in the statistical analysis plan.
Results: Twenty-eight patients received OOC and 12 failed to maintain biochemical response based on the primary endpoint. Seven of these 12 patients discontinued treatment early – 5 due to treatment failure and 2 due to AEs. The remaining 5 patients completed the 36-week protocol on study drug. Of these 5 patients, 4 had IGF-I values between >1.0 and ≤ 1.3 × ULN and 1 completed the study with an IGF-I of 1.7 × ULN with no clinical symptoms. 58.2% of patients in the OOC group met the primary endpoint of maintenance of biochemical response at the end of study using the non-response imputation. Using LOCF imputation, 64.3% (18/28) of patients met this endpoint. Of those completing the study (n = 21), 76.2% maintained response.
Conclusion: CHIASMA OPTIMAL primary endpoint was assessed using the non-response imputation for patients who discontinued treatment early, with a 58.2% response rate. However, when assessing the response rate based on LOCF imputation, or in study completers, similar to other phase 3 studies for acromegaly, the rate was imputed at 64.3% and 76.2%, respectively.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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