CSR Flashcards
How many subjects were submitted for adjudication?
46: (35 tolvaptan and 11 placebo)
What were the demographic and baseline characteristics of the at-risk cohort (meeting adjudication criteria?)
Subjects in the at-risk cohort were older, more female, more Asian, and lower renal function. For the placebo group, at risk were also older and more female, but none were Asian and no difference in renal function.
What was the reversibility of ALT?
All 46 adjudicated subjects (35/35 and 11/11 placebo) resolved to <= 3 x ULN.
For tolvaptan subjects who continued after peak ALT…
…21/35- resolution to <=3X occurred within 4 months for approximately 80% of these subjects.
For tolvaptan subjects who discontinued before peak ALT was reached or within 2 days of reaching peak…
…14/35, resolution to <=3X occurred within 40 days for approximately 80% of these subjects, which was more rapid than for subjects who continued treatment after peaking.
What was the longest time to resolution…
…15.5 months after peaking for a subject who continued therapy, and was approximately 19 months for a subject who discontinued treatment.
What was resolution to <= 3X ULN for placebo subjects?
All 11 placebo subjects evolved in less than 20 days after peak ALT was reached.
What about reversibility to ULN or below?
For the 21 who continued treatment after peak ALT (21/35) resolution to <= ULN occurred within 17 months for approximately 80%.
For those who discontinued IMP before peak or within 2 days..
…14/35, resolution to <=ULN occurred within 3.5 months for 10 out of 14 subjects- 71.4%.
What was the longest time to resolution?
29 months after peaking for a subject who continued therapy, and was approximately 3.5 months for a subject who discontinued treatment.
For placebo subjects…
…resolution to <=ULN was achieved by approximately 80% of placebo subjects within 2.5 months–longest time to resolution was 14 months.
Why were subjects censored and how many?
5 TLV subjects were censored if they did not achieve this degree of resolution as of the last measurement.
What was the reversibility of BT?
The majority (26/35 or 74.3%) did not have BT values above the ULN.
For the (/35 (25.7%) that did have a BT value above ULN…
3 who continued tx after peak BT was reached had resolution to <=ULN within 3 months.
3 were censored.
What is the summary of reversibility?
Resolution to <=3x was generally more rapid for subjects who discontinued tolvaptan treatment (within 40 days) than for subjects who continued tolvaptan treatment 9within 4 months). For those with elevated BT- resolution to ULN is documented for 6 subjects and extrapolated for 2 subjects based on documented resolution of AEs.
