Efficacy and Safety of Teverelix, a New Gonadotrophin Releasing Hormone Antagonist in Patients With Advanced Prostate Cancer. Results From a Phase 2 Multicentre, Open-Label, Pilot Study Investigating an Initial Intramuscular Loading Dose Regimen of Teverelix

MacLean, Carol M.; Ulys, Albertas; Jankevičius, Feliksas; Kaniušas, D.; Drewe, J.; Larsen, Finn Ole

doi:10.1016/s1569-9056(06)60921-4

Cited by 3 publications

(3 citation statements)

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“…Teverelix TFA has previously been shown in phase 2 clinical trials to be effective in the treatment of hormone-sensitive advanced prostate cancer 18,19 and moderate to severe benign prostatic hyperplasia (BPH). 20 A phase 2B clinical trial in advanced prostate cancer is ongoing to test a dosing regimen identified as being likely to be successful based on the data from this phase 1 trial.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic, Safety, and Pharmacodynamic Properties of Teverelix Trifluoroacetate, a Novel Gonadotropin‐Releasing Hormone Antagonist, in Healthy Adult Subjects

MacLean¹,

Godsafe²,

Soto-Forte

et al. 2021

Clinical Pharm in Drug Dev

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Teverelix trifluoroacetate is a decapeptide, gonadotropin‐releasing hormone antagonist that binds competitively and reversibly to gonadotropin‐releasing hormone receptors in the pituitary gland, resulting in immediate suppression of luteinizing hormone and follicle‐stimulating hormone, which in turn causes a very rapid decrease in testosterone production in the Leydig cells of the testes in men and in estradiol in the ovaries in women. This phase 1 clinical study was an open‐label, parallel‐design, single‐center, single‐dose study in older, healthy male subjects. Following injection, teverelix is released into the systemic circulation in a biphasic manner. An initial rapid phase is followed by a slow‐release phase thought to be due to the formation of a depot, which limits the diffusion of teverelix into the blood. The release characteristics differ significantly for the subcutaneous (SC) and intramuscular (IM) routes. Teverelix maximum concentration and exposure increased in an approximately dose‐proportional manner across the 60 to 120 mg SC doses. All 3 pharmacodynamic end points (luteinizing hormone, follicle‐stimulating hormone, and total testosterone) showed reductions that were more prolonged following the 90 mg IM administration compared to 90 mg SC administration.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic, Safety, and Pharmacodynamic Properties of Teverelix Trifluoroacetate, a Novel Gonadotropin‐Releasing Hormone Antagonist, in Healthy Adult Subjects

MacLean¹,

Godsafe²,

Soto-Forte

et al. 2021

Clinical Pharm in Drug Dev

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“…This enables the parenteral (subcutaneous [SC] or intramuscular (IM)) administration of a large amount of peptide in a relatively small volume. The injection of teverelix DP via either the SC or IM route has been shown to result in a rapid (within 1-2 days) suppression of LH, FSH, testosterone (in males) [19,20] and E 2 (in females) [21].…”

Section: Introductionmentioning

confidence: 99%

“…Initial trials with teverelix DP have focused on identifying an effective loading dose and establishing its duration of action [19,20]. In prostate cancer, where the goal is to attain and maintain profound castrate levels of testosterone, the challenge is to deliver sufficiently high initial amounts of peptide into the circulation to compete against endogenous GnRH and occupy pituitary GnRH receptors 100%.…”

Section: Introductionmentioning

confidence: 99%

Safety, Pharmacokinetic and Pharmacodynamic Evaluation of Teverelix for the Treatment of Hormone-Sensitive Advanced Prostate Cancer: Phase 2 Loading-Dose-Finding Studies

MacLean¹,

Ulys

Jankevičius

et al. 2023

Medicina

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Background and objectives: Teverelix drug product (DP) is a gonadotropin-releasing hormone antagonist in development for the treatment of patients with prostate cancer in whom androgen deprivation therapy is indicated. The aim of this paper is to present the results of five Phase 2 studies that assessed the pharmacokinetics, pharmacodynamics, efficacy and safety of different loading dose regimens of teverelix DP. Methods: Five single-arm, uncontrolled clinical trials were conducted in patients with advanced prostate cancer. The five different loading dose regimens of teverelix DP tested were (a) a single 90 mg subcutaneous (SC) injection of teverelix DP given on 3 consecutive days (Days 0, 1 and 2); (b) a single 90 mg intramuscular (IM) injection of teverelix DP given 7 days apart (Days 0 and 7); (c) a single 120 mg SC injection of teverelix DP given on 2 consecutive days (Days 0 and 1); (d) 2 × 60 mg SC injections of teverelix DP given on 3 consecutive days (Days 0, 1 and 2), and (e) 2 × 90 mg SC injections of teverelix DP given on 3 consecutive days (Days 0, 1 and 2). The primary efficacy parameter was the duration of action of an initial loading dose regimen in terms of suppression of testosterone to below the castration level (0.5 ng/mL). Results: Eighty-two patients were treated with teverelix DP. Two regimens (90 mg and 180 mg SC on 3 consecutive days) had a mean duration of castration of 55.32 days and 68.95 days with >90% of patients having testosterone levels < 0.5 ng/mL at Day 28. The mean onset of castration for the SC regimens ranged from 1.10 to 1.77 days, while it was slower (2.4 days) with IM administration. The most common adverse event (AE) was injection site reaction. No AEs of severe intensity were reported. Conclusions: Teverelix DP is safe and well tolerated. Castrate levels of testosterone can be rapidly achieved following the subcutaneous injection of teverelix DP on 3 consecutive days. Streamlining of the administration of the loading dose and identifying a suitable maintenance dose will be investigated in future trials.

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Management of Prostate Cancer: Global Strategies

Alcaraz

2006

European Urology Supplements

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Efficacy and Safety of Teverelix, a New Gonadotrophin Releasing Hormone Antagonist in Patients With Advanced Prostate Cancer. Results From a Phase 2 Multicentre, Open-Label, Pilot Study Investigating an Initial Intramuscular Loading Dose Regimen of Teverelix

Cited by 3 publications

References 0 publications

Pharmacokinetic, Safety, and Pharmacodynamic Properties of Teverelix Trifluoroacetate, a Novel Gonadotropin‐Releasing Hormone Antagonist, in Healthy Adult Subjects

Pharmacokinetic, Safety, and Pharmacodynamic Properties of Teverelix Trifluoroacetate, a Novel Gonadotropin‐Releasing Hormone Antagonist, in Healthy Adult Subjects

Safety, Pharmacokinetic and Pharmacodynamic Evaluation of Teverelix for the Treatment of Hormone-Sensitive Advanced Prostate Cancer: Phase 2 Loading-Dose-Finding Studies

Management of Prostate Cancer: Global Strategies

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