General

Question 1

What was the name of the journal Sprague was published in? What year?

Answer 1

American Journal of Nephrology, 2016

Question 2

(Sprague) How many US sites?

Answer 2

89 US sites

Question 3

(Sprague) - Rayaldee normalized the 25 hydroxyvitamin D greater than 30 what percent of per protocol patients?

Answer 3

95%

Question 4

(Sprague): Rayaldee reduced the PTH by at least 10% in what percentage of patients?

Answer 4

72%

Question 5

(Sprague): how many subjects/what percentage completed the 26 weeks in studies A and B?

Answer 5

354
83%

Question 6

What is the half-life of Rayaldee?

Answer 6

25 days

Question 7

What should the serum calcium be below before initiating therapy?

Answer 7

9.8

Question 8

What’s the Rayaldee maintenance 25D level range?

Answer 8

30 to 100 ng/ml

Question 9

Prior to dose increase what should the serum ca, serum phosphorus and serum 25 be?

Answer 9

Serum calcium should be <9.8 milligrams per deciliter
Serum phosphorus should be <5.5 milligrams oer deciliter
Serum 25D < 100 nanograms

Question 10

(Sprague): Figure 1 (25 D)
What were the 25D levels at the start of the study?
What were the levels in 3-4 weeks?

Answer 10

20 nanograms at start
30 nanograms in 3-4 weeks

Question 11

(Sprague): Fig 1 (25D)
When was steady state reached for the 30 mg dose? What did the vitamin D levels average?

Answer 11

Steady state reached At 12 weeks, vitamin D levels averaged 50-56 ng/ml

Question 12

(Sprague): Fig 1 (25D)

At how many weeks could dose titration occur? What could they titrate to?

Answer 12

Dose titration could occur at the start of week 13. Titration to 60 micrograms.

Question 13

(Sprague): Fig 1 (25D)

Steady-state serum 25D averaged ____ ng/ml and ______ ng/ml for subjects receiving Rayaldee 60 mcg daily.

Answer 13

69 and 67 ng/ml

Question 14

(Sprague): Fig 1 (25D)

What percentage of subjects increased the dose to 60 micrograms per day in the study?

Answer 14

74%

Question 15

(Sprague): Fig 2 (iPTH)

Intent to treat population what percentage of subjects had at least a 30% reduction of PTH irrespective of stage?

Answer 15

33% and 34% had at least a 30% reduction of PTH

Question 16

(Sprague): Fig 2 (iPTH)

What did the PTH level do as 25D increased with Rayaldee treatment?

Answer 16

PTH levels declined gradually but progressively as 25D increased with Rayaldee treatment.

Question 17

(Sprague): Fig 2 (iPTH)

What was the per protocol population percentage of patients having a 30% reduction in PTH?

Answer 17

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

Question 18

(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:

Answer 18

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

Question 19

(Sprague): Fig 4 (CA and phosphorus)

Calcium and phosphorus were similar to what?

Answer 19

Calcium and phosphorus were similar to placebo (.2 versus .1)

Question 20

(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:

Answer 20

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

Question 21

(Sprague): What was the study design?

Answer 21

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).

Question 22

What are the key factors driving growth of CKD?

Answer 22

Obesity, hypertension, diabetes

Question 23

CKD affects more than what percentage of the US population and approximately how many people?

Answer 23

6% or 20 million

Question 24

SHPT affects what percentage of stage 3 and stage 4 patients?

Answer 24

40% of stage 3 and 82% of stage 4 patients

Question 25

Vitamin D insufficiency affects an estimated what percent of patients with stage 3 and 4 CKD?

Answer 25

71% of stage 3 and 83% of stage 4

Question 26

Vitamin D insufficiency is defined as

Answer 26

Low 25 hydroxyvitamin D less than 30. Increased expression of Cyp24A1 which catabolizes 25 hydroxyvitamin D to 24/25 dyhydroxyvitamin D.

Question 27

SHPT is characterized by

Answer 27

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.

Question 28

Fill in the blank:

(Sprague): At 12 weeks dose titration could occur to _____ mg.

Answer 28

60 micrograms

Question 29

At 12 week titration on the 60mg vitamin D levels averaged

Answer 29

69 and 67 ng

Question 30

(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.

Answer 30

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.

Question 31

(Sprague):

How many total subjects?

How many subjects in study A?

How many subjects in study B?

Answer 31

429 total subjects.

213 in study A

216 in study B

Question 32

(Sprague): How many subjects/what percent of subjects entered the single 6-month open label extension study?

Answer 32

298 (69%)

Question 33

(Sprague): what was the primary efficacy end point?

Answer 33

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.