FOOD AND DRUG ADMNISTRATION

Center for Drug Evaluation and Research

ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE (AIDAC) MEETING

July 10, 2002

NDA 21-242

Artesunate Rectal Capsules

World Health Organization

Errata Sheet for FDA Briefing Document

  1. Page 22, Table 11: Clinical and parasitological outcomes at 24 hours, according to FDA defined endpoints.

  1. The number of Clinical Failures in the Artesunate arm of Study 005 (in Thailand) should be "10", not "11". Confidence intervals and p-values have been recalculated.
  2. There was a mathematical error in the calculation of the confidence intervals of the 24-hour success rates (clinical and parasitological) for Studies 006 and 007. However, all the other numbers (including the p-values) were correct as reported and have not been changed.

Thus, the proper values in the table are as follows:

 

Location (Study No.)

 

Thailand (005)*

Malawi (006)**

South Africa (007)*

Randomized

Artesunate

Comparator

46

17

87

22

27

9

Excluded

Artesunate

Comparator

5

3

3

0

1

1

Clinical Failures

Artesunate

Comparator

10

4

8

0

1

2

24-hr clinical success rate

Artesunate

Comparator

95% CI Artesunate – Comp.

P –value***

31/41 (76%)

10/14 (71.4%)

(-24.1, 41.1)

0.7358

76/84 (90.5%)

22/22 (100%)

(-24.3, 10.6)

0.2006

25/26 (96%)

6/8 (75%)

(-14.1, 66.8)

0.1310

24-hr parasitological success rate

Artesunate

Comparator

95% CI Artesunate – Comp

P –value***

 

31/41 (76%)

10/14 (71.4%)

(-24.1, 41.1)

0.7358

 

74/84 (88%)

3/22 (13.6%)

(53.3, 90.9)

<0.0001

 

22/26 (84.6%)

2/8 (25%)

(19.3, 93.3)

0.0034

* Rescue was permitted in both arms in these studies

** Rescue was only permitted in the AS arm in this study.

***Exact confidence interval and Fishers Exact Test

  1. Page 26, third paragraph, fourth sentence.

  2. The word "absorption" is to be replaced by the word "present" so that the sentence should read as follows:

    "Other potential reasons for variability in the study include: inconsistencies in rectal absorption, variability in the amount of drug substance present in the dosage form, variability in drug product quality, dissolution rate limitations from the formulation, and individual variability in drug metabolism."

  3. Page 33, second paragraph, third sentence.
  4. There is a typographical error. The sentence should read:

    "The numbers and type of adverse events…"

     

  5. Page 35, first paragraph, Item #2.

The word "Quest" is to be replaced by the word "Quintiles" so that the sentence should read as follows:

"2) Non-clinical WHO-commissioned toxicology studies performed by Quintiles of United Kingdom,"