-controlled trial in adults with travelers’ diarrhea.
Trial 1 (NCT01142089) was conducted at clinical sites in Guatemala and Mexico, and provides theprimary evidence for the efficacy of AEMCOLO. A second active-controlled trial (Trial 2 –NCT01208922) conducted in India, Guatemala and Ecuador, provided supportive evidence for theefficacy of AEMCOLO. Although patients with fever and/or bloody stool at baseline were to beexcluded from both trials, 18 subjects treated with AEMCOLO had fever and bloody diarrhea atenrollment in Trial 2. Stool specimens were collected before treatment and 1 to 2 days following theend of treatment to identify enteric pathogens. The predominant pathogen in both trials was E. coli.
The clinical efficacy of AEMCOLO was assessed using an endpoint of time to last unformed (wateryor soft) stool (TLUS) before achieving clinical cure. The endpoint of clinical cure was defined as twoor fewer soft stools and minimal enteric symptoms at the beginning of a 24-hour period or nounformed stools at the beginning of a 48-hour period. Kaplan-Meier estimates of TLUS for the intentto-treat(ITT) Population, which includes all randomized subjects, in Trial 1 (Figure 1) show that
AEMCOLO significantly reduced the TLUS compared to placebo (p=0.0008).
Figure 1: Kaplan-Meier Estimates of Time to Last Unformed Stool (TLUS) in Trial 1(ITT Population)
Reference ID: 4351115
10
Table 1 displays the median TLUS and th
Table 1 displays the median TLUS and the number of patients who achieved clinical cure for the ITTpopulation in Trial 1. The median duration of diarrhea was significantly shorter in patients treated withAEMCOLO than in the placebo group. More patients treated with AEMCOLO were classified asclinical cures than were those in the placebo group.
Table 1: Clinical Response in Trial 1 (ITT Population)
AEMCOLO
(N=199)
Placebo
(N=65)
Difference P value
Median TLUS (hrs) 46.0 68.0 -22.0 p = 0.0008a
Clinical cure, n (%) 162 (81.4%) 37 (56.9%) 24.5% p =0.0001b
ITT = Intent-to-Treat; TLUS = time to last unformed stool (in hours) a log-rank test. A 95% confidence interval for the difference in medians cannot be computed due to the amount ofcensored observations in the placebo group.
b chi-square test, 95% confidence interval on the difference is (11.3, 37.7).
The results of Trial 2 supported the results presented for Trial 1. In addition, this trial providedevidence that AEMCOLO-treated subjects with fever and/or bloody diarrhea at baseline hadprolonged TLUS. [see Warnings and Precautions (5.1)]
15 REFERENCES
1. Ziv G, Sulman FG. eva luation of rifamycin SV and rifampin kinetics in lactating ewes.Antimicrob Agents Chemother. 1974;5(2):139-142.
16 HOW SUPPLIED/STORAGE AND HANDLING
AEMCOLO delayed-release tablets contain194 mg of rifamycin (equivalent to 200 mg of rifamycinsodium), and are yellow brown, ellipsoidal and film coated. These are packaged in blister cards of 12tablets contained in a cardboard carton. They are supplied as follows:
NDC (71068-001-10) : child resistant box of 12 tablets.
NDC (71068-001-11) : box of 36 tablets
Store at 20° to 25°C (68 to 77°F) excursions permitted to 15 to 30°C (59° to 86°F).
17 PATIENT COUNSELING INFORMATION
Persistent Diarrhea
Inform the patient being treated for travelers’ diarrhea to discontinue AEMCOLO if diarrhea persistsmore than 48 hours or worsens. Advise the patient to seek medical care for fever and/or blood in thesto |
