Cadazolid/ ACT-179811 (AC-0641A301)

Purpose / Objectives

Primary Outcome

To determine whether the clinical response after 10-day oral administration of cadazolid is non-inferior to oral vancomycin, in subjects with CDAD.

Secondary Outcomes

• To determine whether oral administration of cadazolid for 10 days is superior to oral vancomycin in the sustained clinical response of subjects with CDAD.

• To determine whether the resolution of diarrhea (ROD) is more rapid with oral administration of cadazolid compared to vancomycin.

• To determine whether CDAD symptoms as reported by the subject show larger improvements from baseline with oral administration of cadazolid compared to vancomycin.

Diagnosis

• Clostridium-Diarrhoe (English name missing)

Target population

Age

18-99

Inclusion criteria

[...]

• Non-pregnant women of childbearing potential:

A woman is considered to be of childbearing potential unless she meets at least one ofthe following criteria:[...]

• Subject with a diagnosis of mild–moderate or severe CDAD (first occurrence or first recurrence within 3 months of randomization) with
  • Diarrhea, defined as a change in bowel habits with > 3 liquid or UBMs, in the
  24 h prior to randomization,

AND

• Positive C. difficile toxin A and/or B stool test, on a sample collected no more than 72 h prior to randomization using an EIA test approved by the sponsor.

Note 1: If a positive test using an EIA test approved by the sponsor has been performed prior to screening within the time window mentioned above, the test does not need to be repeated and its result will document eligibility. If a non-approved test has been used for the diagnosis of CDAD prior to screening, an EIA test approved by the sponsor must show a positive result on a sample collected no more than 72 h prior to randomization, after the subject has signed the ICF to confirm eligibility.

Note 2: Subjects who have failed at least 72 h of treatment of the current episode with metronidazole, continue to meet the definition of diarrhea without significant clinical improvement in the judgment of the investigator, and remain toxin positive (with a positive stool test done on a sample collected no more than 48 h prior to randomization) may be enrolled in the study. Metronidazole therapy must be stopped prior to first dose of study drug.

 

Exclusion criteria

1.More than one previous episode of CDAD in the 3-month period prior to randomization. 2. Fulminant or life-threatening CDAD as evidenced by the presence of any of the following during the 72 h period prior to randomization:

• Septic shock – a systolic blood pressure (BP) < 90 mmHg or a mean arterial pressure < 70 mmHg in the absence of other causes of hypotension and that persists despite adequate fluid resuscitation
• Peritonitis
• Ileus
• Toxic megacolon
• Significant dehydration based on investigator judgment
• White blood cells count > 30,000 109/L
• Core body temperature > 40 °C

3. Concurrent immediately life-threatening disease or condition (likelihood of death within 72 h).

4. History of inflammatory colitides (e.g., ulcerative colitis or Crohn’s disease, microscopic colitis, collagenous colitis) or chronic abdominal pain or chronic diarrhea of any etiology.

5. Vomiting or other condition that interferes with the ability to take oral medication and subjects with feeding tubes.

[...]

Study design

• Phase III
• Multicenter
• Prospective
• One-arm
• Two-arm
• Double-blind
• Randomized

Intervention

250 mg Cadazolid every 12 hours versus 125 mg Vancomycin every 6 hours

Documents (password protected)

Go to download area

Responsibilities in overall study

Sponsor

ACTELION Pharmaceuticals Ltd.

• Tel. + 41 61 565 64 33

(National) Coordinating Investigator

Prof. Dr. med. Maria J.G.T. Vehreschild (geb. Rüping)