Endo Announces Publication of New AVEED® (testosterone undecanoate) Data in Peer-Reviewed Journal of Clinical Pharmacology; Data Evaluates Dosing Flexibility in Men With Hypogonadism

Endo Announces Publication of New AVEED® (testosterone undecanoate) Data in Peer-Reviewed Journal of Clinical Pharmacology; Data Evaluates Dosing Flexibility in Men With Hypogonadism

PR Newswire

DUBLIN, Jan. 13, 2022

DUBLIN, Jan. 13, 2022 /PRNewswire/ --

 

Endo International plc (NASDAQ:ENDP) announced today the publication of data from a population pharmacokinetic (PK) modeling and simulation study, evaluating potential dosing flexibility of AVEED® (testosterone undecanoate) in hypogonadal males. The objective of this population PK analysis was to assess the potential impact of a more frequent dose regimen of testosterone undecanoate (8 weeks vs. 10 weeks) on exposure parameters of clinical interest. The current FDA-approved recommended dose of AVEED® is 3 mL (750 mg) injected intermuscularly, followed by 3 mL (750 mg) injected after 4 weeks, then 3 mL (750 mg) injected every 10 weeks thereafter.1

The findings from this PK model and simulation were published in The Journal of Clinical Pharmacology. See online version of the article.

AVEED® is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

AVEED® should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis.

Male hypogonadism, an impairment of testosterone production or other physiological activity of the gonads, can be due to a primary testicular disorder (primary hypogonadism) or secondary to dysfunction of the hypothalamic-pituitary-testicular axis (hypogonadotropic hypogonadism).2 The normal range of serum testosterone level is between 300 ng/dL and 1,000 ng/dL. Safety and efficacy of AVEED® in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. Safety and efficacy of AVEED® in males less than 18 years old have not been established.1

While the majority of hypogonadal men treated with AVEED® maintain normal serum testosterone levels for the full 10 weeks with the currently approved regimen, there is a small portion of patients who experience a decrease in testosterone levels prior to the next dose. The modeling data indicate that for those patients who experience a trough testosterone level below 300 ng/dL while on treatment, a different dosing regimen with shortened injection interval may help them maintain serum testosterone levels within the normal range between dosing. Further clinical prospective study will be needed to assess the clinical relevance of these predictions.

About the PK Model and Simulation 
The population PK model was developed using data from a Phase 3, single-arm, open-label study (Study IP157-001, Part C of a 5-part study - ClinicalTrials.gov identifier: NCT00467870).3,4 In that study, men with hypogonadism received testosterone undecanoate 750 mg in 3 mL of castor oil and benzyl benzoate (250 mg/mL) injected IM into the buttocks at baseline, at 4 weeks, and then every 10 weeks for up to 84 weeks.

Data included in the PK model were from 130 men with hypogonadism enrolled in the original Phase 3 study, who had 2360 total testosterone concentration measurements. The objective of the population PK model was to assess the currently-approved regimen (750 mg at start of therapy, at 4 weeks, and then every 10 weeks as maintenance) vs. an alternative dosing regimen (750 mg at start of therapy, at 4 weeks, and then every 8 weeks as maintenance) on PK parameters of testosterone exposure and the percentage of patients achieving testosterone concentrations within the normal physiologic range.

Of these men, 117 patients were included in the PK population—matched in size and demographics for the 500 study simulations that were part of the final model validation. Each of these 500 studies simulated the 10-week and 8-week regimen with testosterone concentrations simulated every 48 hours following doses 1, 2, 3, 4 and 10.

This PK model predicted both Cavg and Ctrough would be increased by 11% for the 8-week regimen, whereas Cmax would be increased to a lesser extent (5%), with a low likelihood of patients exceeding a maximum concentration of >2500 ng/dL. More importantly, the percentage of patients with Ctrough >300 ng/dL increased from 66.7% with the 10-week regimen to 76.1% with the 8-week regimen; and the 8-week regimen was not associated with an increase in the percentage of patients with Cmax >2500 ng/dL.

IMPORTANT SAFETY INFORMATION about AVEED® 

WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS
   

Serious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life‐threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection. These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose.
  

Following each injection of AVEED®, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis.


Because of the risks of serious POME reactions and anaphylaxis, AVEED® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the AVEED® REMS Program.

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

Notable requirements of the AVEED® REMS Program include the following:

Further information is available at www.AveedREMS.com or call 1–855–755–0494.

ADVERSE REACTIONS  
AVEED® was evaluated in an 84–week clinical study using a dose regimen of 750 mg (3 mL) at initiation, at 4 weeks, and every 10 weeks thereafter in 153 hypogonadal men. The most commonly reported adverse reactions (≥2%) were: acne, injection site pain, prostate specific antigen increased, hypogonadism, estradiol increased, fatigue, irritability, hemoglobin increased, insomnia, and mood swings.

In the 84–week clinical trial, 7 patients (4.6%) discontinued treatment because of adverse reactions. Adverse reactions leading to discontinuation included: hematocrit increased, estradiol increased, prostatic specific antigen increased, prostate cancer, mood swings, prostatic dysplasia, acne, and deep vein thrombosis.

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

DRUG ABUSE AND DEPENDENCE  
AVEED® contains testosterone undecanoate, a Schedule III controlled substance in the Controlled Substances Act.

About Endo International plc  
Endo (NASDAQ: ENDP) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring the best treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at www.endo.com or connect with us on LinkedIn.

Forward-Looking Statement 
This press release contains certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation, including, but not limited to statements regarding the potential progress, timing and results of clinical studies and trials, research and development outcomes, product safety, efficacy, effectiveness, adverse reactions, market and product potential and product availability. Statements including words such as "believes," "expects," "anticipates," "intends," "estimates," "plan," "will," "may," "look forward," "intend," "guidance," "future" or similar expressions are forward-looking statements. Because these statements reflect Endo's current views, expectations and beliefs concerning future events, they involve risks and uncertainties. Although Endo believes that these forward-looking statements and information are based upon reasonable assumptions and expectations, readers should not place undue reliance on them, or any other forward-looking statements or information in this news release. Investors should note that many factors, as more fully described in the documents filed by Endo with the Securities and Exchange Commission and with securities regulators in Canada on the System for Electronic Document Analysis and Retrieval, including under the caption "Risk Factors" in Endo's Form 10-K, Form 10-Q and Form 8-K filings, and as otherwise enumerated herein or therein, could affect Endo's future results and could cause Endo's actual results to differ materially from those expressed in forward-looking statements contained in this communication. The forward-looking statements in this press release are qualified by these risk factors. Endo assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise, except as may be required under applicable securities laws.

Please see accompanying full Prescribing Information, including Boxed Warning.

References

  1. AVEED® (testosterone undecanoate) injection, for intramuscular use CIII [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.; 2018.
  2. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018; 103(5): 1715-1744.
  3. Morgentaler A, Dobs AS, Kaufman JM, et al. Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study. J Urol. 2008; 180(6): 2307-2313.
  4. Wang C, Harnett M, Dobs AS, et al. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial. J Androl. 2010; 31(5): 457-465.

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