MIPLYFFA (arimoclomol citrate)

Arimoclomol exhibited linear and dose proportional pharmacokinetics following oral administration of doses ranging from 62 to 372 mg (three times the maximum recommended dosage) three times a day in healthy subjects. The plasma C max and AUC 0-8hr of arimoclomol at the 248 mg dose (two times the maximum recommended dosage) are summarized in Table 2 .

Table 2Geometric mean (CV%) Pharmacokinetic Parameters of Arimoclomol Following Oral Administration in Healthy Subjects Plasma PK Parameters 248 ...

Safety and effectiveness of MIPLYFFA were assessed in Trial 1, a randomized, double-blind, placebocontrolled, 12-month trial in patients 2 to 19 years of age who had a molecularly confirmed diagnosis of NPC (NCT02612129). Fifty patients were randomized 2:1 to treatment with weight-adjusted MIPLYFFA (31 to 124 mg) or placebo orally three times per day. The randomization was stratified by miglustat use status at baseline. Efficacy assessments, including the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score, were performed at baseline and every 3 months until 12 months of treatment....

The following clinically significant adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warning and Precautions ( 5.1 )]. Increased Creatinine without Affecting Glomerular Function [see Warnings and Precautions ( 5.3 )]. Most common adverse reactions (≥15%) are: Upper respiratory tract infection, diarrhea, and decreased weight. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zevra Therapeutics, Inc. at toll-free phone 1-844-600-2237 or FDA...

None. None. ( 4 )

Hypersensitivity Reactions : Urticaria and angioedema have been reported. Discontinue MIPLYFFA in patients who develop these adverse reactions. ( 5.1 ) Embryofetal Toxicity : May cause fetal harm. Advise pregnant females of the potential risk to the fetus and consider pregnancy planning and prevention. ( 5.2 ) Increased Creatinine without Affecting Glomerular Function: Mean increases in serum creatinine of 10-20% have been reported. Use alternative measures to assess renal function which are not...

7 DRUG INTERACTIONS Substrates of the Organic Cationic Transporter 2 (OCT2 substrates) : Monitor for adverse reactions and reduce the dosage of the OCT2 substrate. ( 7.1 ) 7.1 Effect of MIPLYFFA on Other Drugs Arimoclomol is an inhibitor of the organic cationic transporter 2 (OCT2) transporter and may increase the exposure of drugs that are OCT2 substrates [see Clinical Pharmacology ( 12.3 )] . Wh...