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Pharmacokinetics and Safety of Long-Acting Release Formulations of Pasireotide (SOM230) in a Male Population Who Are Hyperendemic Hepatitis B/C and Chronic Kidney Disease: An Open-Label, Phase I Study

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Abstract

Background

In patients with kidney or hepatic diseases, an increment of circulating pasireotide is also expected. Therefore, this open-label, phase I study aimed to evaluate the pharmacokinetic profiles and safety of subcutaneous (SC) and long-acting release (LAR) intramuscular injections of pasireotide in male Taiwanese volunteers who are hyperendemic hepatitis B/C and chronic kidney disease (CKD).

Methods

A total of 45 male volunteers were randomized to receive one of nine treatment sequences, involving a single subcutaneous injection of 300, 600, or 900 μg pasireotide, a multiple SC injection of the same dosage of pasireotide [300, 600, or 900 μg, twice daily (b.i.d.) for 4 days and a single dose for 1 day], and a single dose of 20, 40, or 60 mg LAR pasireotide intramuscular injection. The pasireotide SC and LAR formulations were prepared and supplied to the study center by Novartis. Pharmacokinetic parameters were assessed from both formulations. All adverse events that occurred in participants throughout the study period, including abnormalities in fasting levels of glucose, insulin, and glucagon, as well as laboratory measurements and electrocardiograms, were recorded.

Results

Analysis of plasma concentration over time revealed a rapid absorption of pasireotide, with a maximal concentration at 0.5 h after SC injection(s) of pasireotide (300–900 µg). Following a single dose of pasireotide LAR (20–60 mg), a sustained release was observed following an initial increase on day 1, a plateau around day 20, and a decline over the next 7 weeks.

Conclusions

Both pasireotide formulations showed dose-proportional pharmacokinetics and 300–900 μg of SC pasireotide and 20–60 mg LAR pasireotide treatment showed favorable safety profiles and was well-tolerated when administered in male Taiwanese volunteers who are hyperendemic hepatitis B/C and CKD.

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Acknowledgements

This study was partly supported by research grant from National Science and Technology Council, Taiwan (Grant number: NSTC 111-2314-B-075-071).

Funding

This study was funded by Novartis Pharmaceutical. This phase I clinical trial was funded by Boehringer Ingelheim, Taiwan.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan, ROC

    Chun-Jui Huang

  2. Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Taipei, 11221, Taiwan, ROC

    Chun-Jui Huang

  3. Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Taipei, 11221, Taiwan, ROC

    Chun-Jui Huang

  4. Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Taipei, 11490, Taiwan, ROC

    Chieh-Hua Lu & Kuang-Chung Shih

  5. Division of Endocrinology and Metabolism, Cheng Hsin General Hospital, No. 45, Cheng Hsin St., Taipei, 11217, Taiwan, ROC

    Kuang-Chung Shih

Authors
  1. Chun-Jui Huang
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Corresponding author

Correspondence to Kuang-Chung Shih.

Ethics declarations

Conflict of interest

Chun-Jui Huang, Chieh-Hua Lu, and Kuang-Chung Shih declare that they have no conflict of interest.

Data availability statements

The datasets used and/or analyzed during the current study are available from the corresponding author on request.

Ethics approval

The trial protocol was approved by the Institutional Review Board of the Tri-Service General Hospital (Approval Number: 098-01-015) on Dec 14, 2009.

Consent to participate

All participants signed a written informed consent form prior to enrollment.

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Not applicable.

Code availability

Not applicable.

Author contributions

Conceptualization, Kuang-Chung Shih; Data Curation, Chun-Jui Huang; Formal Analysis, Chun-Jui Huang, Chieh-Hua Lu, and Kuang-Chung Shih; Writing—Original Draft Preparation, Chun-Jui Huang, Writing—Review & Editing, Chun-Jui Huang, Chieh-Hua Lu, and Kuang-Chung Shih; all authors provided critical feedback and helped shape the research, analysis and manuscript, as well as provided final approval of the manuscript.

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Huang, CJ., Lu, CH. & Shih, KC. Pharmacokinetics and Safety of Long-Acting Release Formulations of Pasireotide (SOM230) in a Male Population Who Are Hyperendemic Hepatitis B/C and Chronic Kidney Disease: An Open-Label, Phase I Study. Eur J Drug Metab Pharmacokinet 48, 665–674 (2023). https://doi.org/10.1007/s13318-023-00854-4

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