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Octreotide SC depot in patients with acromegaly and functioning neuroendocrine tumors: a phase 2, multicenter study

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Abstract

Purpose

Octreotide SC depot is a novel, ready-to-use formulation administered via a thin needle. In a phase 1 study in healthy volunteers, this formulation provided higher bioavailability of octreotide with faster onset and stronger suppression of IGF-1 in healthy volunteers versus long-acting intramuscular (IM) octreotide. This phase 2 study evaluated the pharmacokinetics, efficacy, and safety of octreotide SC depot in patients with acromegaly and functioning NETs, previously treated with octreotide IM.

Methods

Adult patients with acromegaly or functioning NETs treated for ≥ 2 months with octreotide IM [10/20/30 mg every 4 weeks (q4w)] received the last dose of octreotide IM treatment in study period 0 and were randomized 28 days later to receive octreotide SC depot 10 mg q2w, or 20 mg q4w for 3 months (period 1). The primary objective was to characterize the PK profile of octreotide SC depot after each injection vs PK for octreotide IM (period 0).

Results

Twelve patients were randomized to receive octreotide SC depot 10 mg q2w (acromegaly n = 3; NET n = 1) or 20 mg q4w (acromegaly n = 4; NET n = 4). Plasma levels of octreotide were higher with octreotide SC depot as compared to octreotide IM. Adverse events were reported in 6 and 8 patients during period 0 and period 1, respectively; most common in period 1 were gastrointestinal disorders.

Conclusion

Octreotide SC depot provided higher exposure (AUC) than octreotide IM, maintained biochemical control in patients with acromegaly and symptom control in patients with functioning NETs, and was well tolerated with a safety profile consistent with octreotide IM.

ClinicalTrials.gov identifier

NCT02299089.

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Acknowledgements

This study was sponsored by Camurus in collaboration with Novartis. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank all the patients, investigators and nurses who participated in this trial. We thank Mayank Singh, Novartis Healthcare Pvt Ltd for medical editorial assistance with this manuscript.

Funding

This study was sponsored by Camurus in collaboration with Novartis Pharma AG.

Author information

Authors and Affiliations

  1. Department of Medicine 1, Endocrinology, Friedrich-Alexander University Erlangen-Nürnberg, 91054, Erlangen, Germany

    Marianne Pavel

  2. Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Humboldt University, Berlin, Germany

    Marianne Pavel

  3. Hospices Civils de Lyon, Fédération d’Endocrinologie, Université Claude Bernard Lyon 1, HESPER EA 7425, 69008, Lyon, France

    Françoise Borson-Chazot

  4. Rouen University Hospital, INSERM CIC-CRB 1404, Hôpital Charles Nicolle, Rouen Cedex, France

    Anne Cailleux

  5. Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors Bad Berka-ENETS Center of Excellence, Zentralklinik Bad Berka GmbH, Bad Berka, Germany

    Dieter Hörsch

  6. Department of Endocrinology and Metabolism, Universitaetsklinikum Essen, Essen, Germany

    Harald Lahner

  7. Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Naples, Italy

    Rosario Pivonello

  8. Novartis Pharma AG, Basel, Switzerland

    Libuse Tauchmanova & Christelle Darstein

  9. Camurus AB, Lund, Sweden

    Håkan Olsson & Fredrik Tiberg

  10. Physical Chemistry, Lund University, Lund, Sweden

    Fredrik Tiberg

  11. Endocrinology, DiMI and CEBR, University of Genoa, Genoa, Italy

    Diego Ferone

  12. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Diego Ferone

Authors
  1. Marianne Pavel
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  2. Françoise Borson-Chazot
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  3. Anne Cailleux
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  4. Dieter Hörsch
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  5. Harald Lahner
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  6. Rosario Pivonello
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  7. Libuse Tauchmanova
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  8. Christelle Darstein
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  9. Håkan Olsson
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  10. Fredrik Tiberg
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  11. Diego Ferone
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Corresponding author

Correspondence to Marianne Pavel.

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Conflict of interest

MP received honoraria for presentations or advisory board from Novartis, IPSEN, Pfizer, and Lexicon. AC has nothing to disclose. FBC received consulting fees for advisory board from Novartis, Ipsen, Merck Serono, Bayer, and Pfizer; honorarium for speaking from Bayer, HAC, and Genzyme. DH received personal fees from Lexicon Pharma, grants and personal fees from Ipsen Pharma Inc, during the conduct of the study; personal fees from Lexicon Pharma Inc; grants and personal fees from Ipsen Pharma Inc, Novartis Pharma Inc, and Pfizer Pharma Inc, outside the submitted work. HL received consulting fees from Novartis. RP received research grant as principal investigator and co-investigator, and lecturer fee and honoraria from Novartis; research grant as clinical researcher, consulting fees, and honoraria as speaker from Shire; research grant as principal investigator from Ipsen and Pfizer. LT and CD are employees of Novartis. HO and FT are employees of Camurus. DF received consulting fee for lectures or advisory boards, and research funding for preclinical research project from Novartis; received consulting fee for advisory boards, and research funding for preclinical research project from Ipsen.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and applicable local regulations. The study protocol and all amendments were reviewed by the independent ethics committee or institutional review board for each center. All patients provided written informed consent to participate in the study.

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Pavel, M., Borson-Chazot, F., Cailleux, A. et al. Octreotide SC depot in patients with acromegaly and functioning neuroendocrine tumors: a phase 2, multicenter study. Cancer Chemother Pharmacol 83, 375–385 (2019). https://doi.org/10.1007/s00280-018-3734-1

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  • DOI: https://doi.org/10.1007/s00280-018-3734-1

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