General Flashcards
What was the name of the journal Sprague was published in? What year?
American Journal of Nephrology, 2016
(Sprague) How many US sites?
89 US sites
(Sprague) - Rayaldee normalized the 25 hydroxyvitamin D greater than 30 what percent of per protocol patients?
95%
(Sprague): Rayaldee reduced the PTH by at least 10% in what percentage of patients?
72%
(Sprague): how many subjects/what percentage completed the 26 weeks in studies A and B?
354
83%
What is the half-life of Rayaldee?
25 days
What should the serum calcium be below before initiating therapy?
9.8
What’s the Rayaldee maintenance 25D level range?
30 to 100 ng/ml
Prior to dose increase what should the serum ca, serum phosphorus and serum 25 be?
Serum calcium should be <9.8 milligrams per deciliter
Serum phosphorus should be <5.5 milligrams oer deciliter
Serum 25D < 100 nanograms
(Sprague): Figure 1 (25 D)
What were the 25D levels at the start of the study?
What were the levels in 3-4 weeks?
20 nanograms at start
30 nanograms in 3-4 weeks
(Sprague): Fig 1 (25D)
When was steady state reached for the 30 mg dose? What did the vitamin D levels average?
Steady state reached At 12 weeks, vitamin D levels averaged 50-56 ng/ml
(Sprague): Fig 1 (25D)
At how many weeks could dose titration occur? What could they titrate to?
Dose titration could occur at the start of week 13. Titration to 60 micrograms.
(Sprague): Fig 1 (25D)
Steady-state serum 25D averaged ____ ng/ml and ______ ng/ml for subjects receiving Rayaldee 60 mcg daily.
69 and 67 ng/ml
(Sprague): Fig 1 (25D)
What percentage of subjects increased the dose to 60 micrograms per day in the study?
74%
(Sprague): Fig 2 (iPTH)
Intent to treat population what percentage of subjects had at least a 30% reduction of PTH irrespective of stage?
33% and 34% had at least a 30% reduction of PTH
(Sprague): Fig 2 (iPTH)
What did the PTH level do as 25D increased with Rayaldee treatment?
PTH levels declined gradually but progressively as 25D increased with Rayaldee treatment.
(Sprague): Fig 2 (iPTH)
What was the per protocol population percentage of patients having a 30% reduction in PTH?
22% of pts had a 30% reduction after 12 weeks
40% of patients had a 30% reduction after 26 weeks
50% of pts had a 30% reduction after 52 weeks
(Sprague): Fig 3 (response rates)
After six months (26 weeks) when an HCP brings the patient back to check labs this is what they should observe:
72% had at least a 10% reduction in PTH
60% had at least a 20% reduction in PTH
40% had at least a 30% reduction in PTH
(Sprague): Fig 4 (CA and phosphorus)
Calcium and phosphorus were similar to what?
Calcium and phosphorus were similar to placebo (.2 versus .1)
(Sprague): Fig 3 (Response Rates)
After three months (12 weeks), when an HCP brings a patient back to check labs for the first time this is what should be observed using 30 mg:
22% of patients had at least a 30% reduction in PTH
40% of patients had at least a 20% reduction in PTH
60% of patients had at least a 10% reduction in PTH
(Sprague): What was the study design?
Two identical studies (studies A and B) with multicenter, randomized, double blind and placebo-controlled trials conducted for 26 weeks followed by one open label extension for an additional 26 weeks (total exposure to study drug was 52 weeks).
What are the key factors driving growth of CKD?
Obesity, hypertension, diabetes
CKD affects more than what percentage of the US population and approximately how many people?
6% or 20 million
SHPT affects what percentage of stage 3 and stage 4 patients?
40% of stage 3 and 82% of stage 4 patients
Vitamin D insufficiency affects an estimated what percent of patients with stage 3 and 4 CKD?
71% of stage 3 and 83% of stage 4
Vitamin D insufficiency is defined as
Low 25 hydroxyvitamin D less than 30. Increased expression of Cyp24A1 which catabolizes 25 hydroxyvitamin D to 24/25 dyhydroxyvitamin D.
SHPT is characterized by
Excessive (high) parathyroid hormone, vitamin D insufficiency (low), phosphate (high ) retention, elevated (high) FGF23, reduced (low) serum total 1.25 hydroxy vitamin D and low calcium.
Fill in the blank:
(Sprague): At 12 weeks dose titration could occur to _____ mg.
60 micrograms
At 12 week titration on the 60mg vitamin D levels averaged
69 and 67 ng
(Sprague): fill in the blank
The dose was increased to ___ μg at the start of week 13 if PTH was ____ pg/mL (the upper limit of the laboratory reference range), serum total 25-hydroxyvitamin D was ___ ng/mL, and serum calcium was ____ mg/dL.
Dose increased to 60 mg,
if PTH was < 70 pg/ml,
Serum 25-hydroxyvitamin D was <65 ng/ml,
Serum calcium was <9.8 mg/dl.
(Sprague):
How many total subjects?
How many subjects in study A?
How many subjects in study B?
429 total subjects.
213 in study A
216 in study B
(Sprague): How many subjects/what percent of subjects entered the single 6-month open label extension study?
298 (69%)
(Sprague): what was the primary efficacy end point?
The number and percent of subjects in the intent to treat population (ITT) that attained a mean decrease greater than or equal to 30% in plasma iPTH from pretreatment baseline to the efficacy assessment period (EAP) defined as the last 6 weeks of the 26 and 52 week treatment periods.
