Table 1.

Outline of clinical trial protocol.

Parameters	Treatment period (weeks)
	Pre	PYR treatment 25 mg/day			50 mg/day	75 mg/day	100 mg/day	Post
	−2 to 0	1	2–3	4	5–8	9–12	13–16	17–18
General
Medical history	✓	✓		✓	✓	✓	✓	✓
Pregnancy test for woman of child-bearing potential	✓	✓		✓		✓
Height	✓	✓		✓		✓
Body weight	✓	✓		✓		✓
Concomitant meds querya	✓	✓	Weekly	✓	Weekly	✓	Weekly	Weekly
Safety assessment
Physical exam including vital signsb	✓	✓		✓	8th wk	12th wk	16th wk	18th wk
Adverse event querya	✓	✓	Weekly	✓	Weekly	Weekly	Weekly	Weekly
Clinical pathologyc	✓			4th wk		12th wk	16th wk	18th wk
Urinalysis	✓			4th wk	8th wk	12th wk	16th wk	18th wk
Efficacy assessment
Plasma and leukocyte Hex A and B, β-glucuronidase and acid phosphatased	✓	✓	Weekly	✓	Weekly	Weekly	Weekly	Weekly
Reserve bloods for measurement of GM2e	✓	✓		✓	✓	✓	✓	✓
Reserve bloods for measurement of PYRe	✓	✓	Weekly	✓	Weekly	Weekly	Weekly	Weekly

^aConcomitant meds query and adverse event query may be done by telephone.

^bPulse rate, respiratory rate, blood pressure, and temperature.

^cClinical pathology can be done at a local lab, includes chemistry, hematology and coagulation. Renal function will be assessed utilizing the Cockcroft–Gault formula and the serum creatinine.

^dThese measurements must be done at least 3 times at intervals of not less than 1 week BEFORE starting PYR. The last measurement can be done on the same day as PYR treatment is started, before the patient receives the first dose of the drug.

^eThe total volume of blood needed is estimated on the basis of the needs for lysosomal enzyme assays, PYR assays, and the safety labs: Enzyme assays, 10 mL; PYR assays, 5 mL; Safety labs, 15 mL.