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13570411000001108

Medicine Compliance Aid Stability

Restandol TestocapsMerck Sharp & Dohme Ltd

Merck Sharp & Dohme Ltd
Restandol Testocaps
Capsules 40mg
R2 · Red 2Drug is not suitable for CAs due to theoretical reasons that cannot be mitigated.
Unsuitable
Capsules are sensitive to moisture and will become sticky if removed from their packaging. Protect from light.
19 February 2015

New Medicines

Tlando Hypogonadism in men

Information

Tlando
New formulation
Lipocine
Lipocine

Development and Regulatory status

None
None
Pre-registration (Filed)
Jan 21Pre-registration (Filed)
Dec 20FDA grants tentative approval, for conditions associated with a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired). In granting tentative approval, the FDA has concluded that TLANDO has met all required quality, safety and efficacy standards necessary for approval. TLANDO is not eligible for final approval and marketing until the expiration of the exclusivity period previously granted to Clarus Therapeutics, with respect to Jatenzo®, which expires on 27/3/22 [16].
Feb 20FDA accept resubmitted NDA and assign a PDUFA date of August 28, 2020 [15].
Jan 20Lipocine report that following Post Action meeting and written feedback, US FDA have indicated their approach to addressing the single remaining deficiency through reanalysis of existing data appears to be a reasonable path forward. Lipocine plans to re-submit Q1 20 [15].
Nov 19Not approved in US - in a CRL, FDA said the efficacy trial did not meet the three secondary endpoints for maximal testosterone concentrations [14].
May 19US FDA accept re-submitted NDA, for testosterone undecanoate as testosterone replacement therapy in adult males for conditions associated with a deficiency of endogenous testosterone (hypogonadism). The FDA has assigned a PDUFA of 9/11/19 [13].
May 18Not approved in the US - in a complete response letter, FDA said the treatment could not be approved in its current form [12]
Nov 17 following submission of further data, the FDA has extended the review period for LPCN1021 (Tlando) and has set a new target action date of 8th May 2018. The Bone, Reproductive and Urologic Drugs Advisory Committee meeting to discuss the drug remains unchanged [11].
Oct 17Tlando (LPCN1021) will be discussed by a FDA Bone, Reproductive and Urologic Drugs Advisory Committee meeting on 10th January 2018 [10].
Aug 17 Lipocine announced the resubmission of the NDA for LPCN 1021 in adult males for hypogonadism. The NDA resubmission was based on the efficacy data of the dosing validation study, an integrated safety set from all previously conducted clinical trials, including 52-week safety results from the PIII SOAR study. The FDA has set a PDUFA date of 8 Feb 2018 [9].
Jun 16Lipocine receives a complete response letter from the US FDA. In the letter, the FDA outlined deficiencies related to the dosing algorithm for the label and specified that the proposed titration scheme for clinical practice was significantly different from the titration scheme used in the PIII trial [9].
Oct 15The FDA has accepted for filing NDA for LPCN 1021. [8]
Sep 15Lipocine Inc. announced that it has submitted an NDA to the US FDA for LPCN 1021 as testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (hypogonadism). The NDA filing is supported by results from the Study of Oral Androgen Replacement (SOAR, NCT02081300) pivotal Phase 3 clinical study [7].
Jul 15Filing of a New Drug Application with the US FDA is expected in the second half of 2015 [6].
Jul 15Lipocine announced that they remain on track to announce one-year safety data from the pivotal PIII study by the end of June 15 and to file an NDA for US FDA approval in the second half of 2015 [5].
Dec 14Lipocine receives confirmation from the US FDA that the design of the SOAR PIII clinical study is currently acceptable for filing a NDA. The FDA reiterated the primary efficacy endpoint required for approval being 75% of subjects with a Cavg for serum testosterone in the normal range with the lower bound of the two-sided 95% confidence interval being >65%. The FDA did not identify any additional clinical studies that would be required for NDA filing, but did state that should any safety signal become apparent during analysis of SOAR, it is possible that additional data may be required. Lipocine plan to file for NDA during Q of 2015 [2].

Category

An orally administered, twice-daily testosterone undecanoate product
The crude incidence rate of symptomatic androgen deficiency was 12.3% per 1000 person-years and increased with age: 5.9%, 11.2%, and 23.3% per 1000 person-years in men who were in their 40s, 50s, and 60s, respectively, at baseline [1].
Hypogonadism in men
Oral

Trial or other data

Sep 15The SOAR study met its primary efficacy endpoint by successfully restoring testosterone levels to the normal range in 88% of pts. In addition, 85% of pts reached their final dose with no more than one dose titration. LPCN 1021 treatment was well tolerated with no hepatic, cardiac, gastrointestinal or drug related serious adverse events [7].
Jul 15Lipocine announced top-line 52-week safety results from the pivotal III SOAR (n=314) study. Overall, LPCN 1021 was well tolerated with no hepatic, cardiac or drug-related adverse effects (AE’s) reported. The adverse event profile for LPCN 1021 was comparable to the active control, Androgel® 1.62%. The only AE´s occurring in > 5% of pts with either LPCN 1021 or the active control were upper respiratory tract infection (5.2% with LPCN 1021 and 5.8% with active control) and fatigue (2.4% with LPCN 1021 and 6.7% with active control) [6].
Jun 15 Lipocine announces successful completion of food effect study for LPCN 1021. The study was an open-label, randomised, 4-period, 4-treatment, crossover, single-dose study evaluating bioavailability and pharmacokinetics of LPCN 1021 as a function of meal and meal fat content in 14 hypogonadal males. Pts received a single LPCN 1021 oral dose of 225 mg testosterone undecanoate under fasted conditions and ~30 minutes following an 800 to 1000 calorie meal which was either low, moderate or high in fat. Topline results indicate that bioavailability of testosterone from LPCN 1021 is not affected by changes in meal fat content and consistent, predictable therapeutic levels of testosterone when administered with a meal [5].
May 14PIII SOAR (NCT02081300) study is ongoing but no longer recruiting pts. It is still expected to complete in Dec 15 [4].
Feb 14SOAR (Safety and Efficacy of Oral LPCN 1021 in Men with Low Testosterone or Hypogonadism; NCT02081300) study begins. SOAR is a PIII, active-controlled, safety and efficacy trial of oral testosterone undecanoate (LPCN 1021) in hypogonadal men. Men (n=315) were allocated to receive either oral testosterone undecanoate (225 mg BD titrated up to 300 mg BD or down to 150mg BD based on serum Testosterone level at Week 3 and 7) or topical testosterone gel 1.62 % (dosed at 40.5mg OD titrated down to 20.25 mg or up to 81 mg based on serum Testosterone on days 14 and 28). The key primary outcome measure will be the proportion of LPCN 1021-treated pts who achieve a total testosterone concentration [Cavg] between 300 - 1140 ng/dL following 13 weeks of treatment. Change from baseline in pt reported outcomes for LPCN 1021 (i.e., International Prostate Symptom Score [I-PSS], Psychosexual Daily Questionnaire [PDQ], Short Form-36 Questionnaire [SF-36]) will also be assessed as well as incidence of adverse effects. The estimated primary completion date is December 2015 [2,3].