OR34-5 Efficacy and Pharmacokinetics of LPCN 1021, a Novel Oral Testosterone Replacement Therapy (TRT), in Hypogonadal Men: Study of Androgen Replacement (SOAR)

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR34-Testosterone Replacement Therapy: Risks and Benefits
Saturday, March 7, 2015: 11:30 AM-1:00 PM
Presentation Start Time: 12:30 PM
Room 6A (San Diego Convention Center)
Christina Wang1, Anthony DelConte, MD2, Jed C. Kaminetsky, MD3, Martin M. Miner, MD4, Pavan Rajendra Yadav1, Srinivasan Venkateshwaran5, Nachiappan Chidambaram5, Satish Nachaegari5, Mahesh Patel5 and Adrian S Dobs, MD, MHS6
1Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, 2Saint Joseph’s University, Philadelphia, PA, 3University Urology Associates, New York, NY, 4Brown University and the Miriam Hospital, Providence, RI, 5Lipocine, Inc., Salt Lake City, UT, 6Johns Hopkins University School of Medicine, Baltimore, MD
Introduction: TRT is indicated for treating hypogonadal men with low serum testosterone (T) levels and related symptoms. However, T products administered as topical or depot formulations are associated with inadvertent T transfer, messy application, poor retention rates, and superphysiologic T levels in some patients. There is a need for T formulations that are more user friendly, limit blood level dose excursions, and avoid T transdermal transfer. LPCN 1021 is a novel oral T undecanoate formulation being assessed in a Phase 3 trial that may avoid some of the undesirable attributes of non-oral T formulations.

Methods: SOAR is a randomized, active-controlled, 2-arm, 12-month, open-label, multicenter, dose-titration trial that included 18- to 80-year-old hypogonadal (T <300 ng/dL on 2 separate days) men. Participants were randomized to either oral LPCN 1021 (n=210) or Androgel® 1.62% (n=105). The starting dose was 225 mg LPCN 1021 BID taken with a meal. The dose could be titrated up (eg, if T Cave,24h <300 mg/dL) or down (eg, if T Cmax was >1500 mg/dL) at weeks 4 and 8 based on 24 h PK. Efficacy was assessed on week 13 based on T Cave,24h from serum samples collected over 24 h for T assayed by LC-MS/MS. Analysis was conducted using the Efficacy Population Set (subjects with ≥1 PK profile and no significant protocol deviations; N=152 LPCN 1021).

Results: LPCN 1021 reliably restored and maintained T levels in the eugonadal range (300-1140 ng/dL) in 88% of hypogonadal men (lower bound 95% CI=81.9%). Mean T Cave,24h value was 447±166 ng/dL, consistent with other non-oral TRT therapies. There was no significant dose timing effect (eg, AM vs PM), suggesting consistent intra-day performance. Overall variability was low (37% CV for Cave,24h). 82.9% of subjects had serum T peak (Cmax) <1500 ng/dL, <5% had Cmax 1800-2500 ng/dL, and only 2% had serum T levels >2500 ng/dL, and those cases were sporadic, transient, and isolated, with no associated clinical events. 85% of subjects required ≤1 dose adjustment, suggesting a safe and effective titration algorithm. 

Conclusions: LPCN 1021 is an orally administered TRT product with acceptable Cave and Cmax excursions, consistent with US FDA targets met by other non-oral TRT products. LPCN 1021 may improve patient adherence as a generally safe, effective, and more convenient option compared to topical, transdermal, injectable, or implanted TRT products.

Disclosure: CW: Clinical Researcher, Clarus, Consultant, Clarus, Clinical Researcher, Lipocine, Inc., Clinical Researcher, Antares, Clinical Researcher, Prolor, Consultant, Lipocine, Advisory Group Member, TesoRx. AD: Consultant, Lipocine, Inc.. JCK: Principal Investigator, AbbVie, Principal Investigator, Lipocine, Inc., Principal Investigator, Ferring Pharmaceuticals, Principal Investigator, Clarus, Principal Investigator, Antares, Consultant, Antares, Principal Investigator, Auxillium, Consultant, Auxillium, Speaker, Auxillium. MMM: Clinical Researcher, NERI, Clinical Researcher, Forest, Consultant, AbbVie, Consultant, Lipocine, Inc., Consultant, Repros. SV: Employee, Lipocine, Inc.. NC: Employee, Lipocine, Inc.. SN: Employee, Lipocine, Inc.. MP: Employee, Lipocine, Inc.. ASD: Consultant, AbbVie, Advisory Group Member, AbbVie, Advisory Group Member, Endo Pharmaceuticals, Advisory Group Member, Lipocine, Inc., Clinical Researcher, Endo Pharmaceuticals, Clinical Researcher, Clarus. Nothing to Disclose: PRY

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Sources of Research Support: Lipocine, Inc.