Miacalcin

Calcitonin (Miacalcin , Novartis) 4-8 units/kg Hours Hours 1-2 mg/dL... 

Calcitonin (Miacalcin) Teriparatide (1-34 units, Forteo) 200 units intranasal daily, alternating nares every other day 20 meg subcutaneously daily for up to 2 years... 

Calcitonin (Fortical, Miacalcin) Calcitriol (Rocaltrol, Calcijex)... 

Calcitonin (Miacalcin, Miacalcin Nasal Spray) is a synthetic 32-amino acid polypeptide that is identical to salmon calcitonin. Salmon calcitonin is more potent than human calcitonin because of its higher affinity for the human calcitonin receptor and its slower metabolic clearance. Administration is by subcutaneous or intramuscular injection or by nasal spray. The absorption of the nasal form is slower than that of the parenteral routes. 

Novartis (2002). Miacalcin (Calcitonin-Salmon) T2002-84 89018101. Available at www. http //www.pharma.us.novartis.com/product/pi/pdf/miacalcin injection.pdf search = %22 Miacalcin%20(Calcitonin-Salmon)%20T2002-84%2089018101%22 downloaded 10/04/ 2006. 

Brand Name(s) Calcimar, Cibacalcin, Fortical, Miacalcin, Miacalcin Nasal CfiemicalClass Polypeptide hormone... 

Nasal Spray (Fortical, Miacalcin Nasal) 200 international units/activation (calcitonin-salmon). 

Parenteral (Calcimar, Miacalcin, Salmonine) 200 IU/mL for injection Cinacalcet (Sensipar)... 

Anticholinergics Endocrine and metabolic agents Antimigraine Atrovent Miacalcin Migranal... 

Miacalcin Nasal Spray. Novartis Pharmaceutical Corp. East Hanover, NJ (1998). Package Insert. 

Calcitonin Human calcitonin (Cibacalcin) Salmon calcitonin (Calcimar, Miacalcin) Mimic the effects of endogenous calcitonin and increase bone formation in conditions such as Paget disease and osteoporosis also used to lower plasma calcium levels in hypercalcemic emergencies... 

Comparability Program Fortical and Miacalcin NS differed in certain aspects, such as the use of recombinant versus synthetic salmon calcitonin and the use of different types and amounts of excipients. Given these differences, Unigene was required to submit data to establish that the findings of safety and efficacy for Miacalcin were relevant to Fortical (i.e., contain the same active ingredient and have comparable bioavailability) and that the formulation differences did not impact previous clinical profile [26,27],... 

Physicochemical Analysis Salmon calcitonin is a 32-amino-acid, nonglycosylated peptide hormone. It is structurally simple, possessing limited secondary structure and a single disulfide bond. The physicochemical characterization studies demonstrated that the primary and secondary structure of Fortical s recombinant salmon calcitonin (sc) was identical to that of Miacalcin s synthetic sc or naturally occurring sc. Further, the tertiary structures of the three were indistinguishable. 

Nonclinical PK/T V The pharmacokinetic profile of Fortical by different routes of administration was compared to Miacalcin, demonstrating similarity in PK profiles between the synthetic and recombinant peptides and toxicity results (28-day rat intranasal toxicity study) were acceptable, particularly in light of clinical safety data. 

Fortical s PD equivalence was shown in a double-blind, active-controlled, 24-week study in 134 postmenopausal women randomized to Fortical (200IU per day) or Miacalcin (200IU per day). The primary outcome measure was change in serum beta-CTx from baseline. The results fell within prespecified PD equivalence limits (-0.08 to 0.06ng/mL equivalence margin of 0.2ng.mL) and indicated Fortical was not inferior to Miacalcin. 

Fortical s PK equivalence was assessed by comparing the relative bioavailability of Fortical to Miacalcin in a multidose, crossover study of 47 healthy female volunteers. Results indicated that Fortical was slightly more bioavailable than Miacalcin, but given the demonstration of similar PD activity, this difference were not considered to be clinically significant. 

Conclusion to Case Study 1 On August 12,2005, the FDA approved Unigene s 505(b)(2) application for Fortical for the same indication as Miacalcin NS [26,27], In the FDA s analysis no statistically and/or clinically significant differences were noted in any aspect of the comparability profile, including clinical performance, and Fortical was approved. 

On February 17,2004, Nastech Pharmaceutical Company announced its filing of an ANDA for a salmon calcitonin nasal spray drug product for the treatment of postmenopausal osteoporosis. As with Fortical, Novartis s Miacalcin was cited as the reference listed drug however, Nastech chose to submit an ANDA via the 505(j)(l) route, rather than a 505(b)(2) application. 

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