Clinical trial NCT03341767 (phase 2, status: terminated)
Conditions: cryptosporidiosis
ICD codes: A07.2
Drugs: clofazimine, placebo
SMILES: CC(C)N=C1C=C2N(C3=CC=C(Cl)C=C3)C3=C(C=CC=C3)N=C2C=C1NC1=CC=C(Cl)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    insufficient accrual rate
  
Eligibility criteria:

        Part A:

        Inclusion Criteria:

          -  Male or Female, Aged 18-65 years old, HIV positive, Cryptosporidium positive by qPCR.

          -  HIV infection and on stable anti-retroviral therapy treatment for at least 2 weeks

          -  Weight >78 lbs/35.4 kg

          -  Presents with diarrhea defined as a condition of three or more loose stools per day
             that has persisted for 3 days or longer

          -  If female, either not of reproductive potential (post-menopause, or status-post
             surgical sterilization) or using highly effective contraception (<1% failure, e.g.,
             intrauterine contraceptive device in place or using injectable contraception) or
             willing to begin highly effective contraception (probably injectable contraception)
             and continue for the presumed exposure period of Clofazimine (54 days after initiation
             of treatment)

          -  Willing and able to provide signed written informed consent or witnessed oral consent
             in the case of illiteracy, prior to undertaking any trial-related procedures

        Exclusion Criteria:

          -  Any condition for which participation in the study, as judged by the investigator,
             could compromise the well-being of the subject or prevent, limit or confound protocol
             specified assessments

          -  Fever >38.0˚C at presentation

          -  Subjects will be screened for evidence of active tuberculosis based on sputum
             production, fever and chest x-ray. Those with sputum production will be tested by Acid
             Fast Bacilli stain of sputum smear and/or by GeneXpert testing. Those with positive
             sputum or chest x-ray suggestive of tuberculosis will be excluded from this study and
             referred for treatment.

          -  Is critically ill, or in the judgment of the investigator has a prognosis that could
             lead to imminent mortality within 60 days or compromise participation in the trial or
             endanger the subject by entering the trial.

          -  History of allergy or hypersensitivity to Clofazimine.

          -  Significant cardiac arrhythmia requiring medication.

          -  Electrocardiogram exclusions based on the means from triplicate electrocardiograms
             performed on Day -1:

               1. Marked prolongation of QT/QTc interval, e.g., confirmed demonstration of QTcF or
                  QTcB interval >450 ms

               2. Pathological Q waves (defined as >40 ms or depth >0.4 to 0.5mV);

               3. Electrocardiogram evidence of ventricular pre-excitation

               4. Electrocardiogram evidence of complete or incomplete left bundle branch block or
                  right bundle branch block

               5. Electrocardiogram evidence of second or third degree heart block

               6. Intraventricular conduction delay with QRS duration >120 ms

               7. Bradycardia as defined by sinus rate <50 bpm.

          -  History of additional risk factors for Torsade de Pointes, e.g., heart failure;
             bradycardia with HR<50 bpm, untreated hypothyroidism, hypokalemia <3.0 mEq/L

          -  Family history of long QT syndrome

          -  Use of concomitant medications that markedly prolong the QT/QTc interval or are
             predicted to have drug-drug interactions with Clofazimine that may lead to toxicity
             from the partner drug including Amiodarone, Amprenavir, Atazanavir, Bedaquiline,
             Bepridil, Chloroquine, Chlorpromazine, Cisapride, Clarithromycin, Cyclobenzaprine,
             Darunavir, Delamanid, Disopyramide Dofetilide, Domperidone, Droperidol, Erythromycin,
             Fosamprenavir, Halofantrine, Haloperidol, Ibutilide, Indinavir, Levomethadyl,
             Lopinavir, Mesoridazine, Methadone, Nelfinavir, Pentamidine, Pimozide, Procainamide,
             Quinidine, Ritonavir, Simiprinivir, Sotalol, Sparfloxacin, Thioridazine, or Tiprinivir

          -  Pregnant and lactating women (screening pregnancy test for females and pregnancy test
             at the discharge follow up visit)

          -  Use of systemic corticosteroids or anti-cryptosporidial treatments within the 28 days
             preceding Day -1

          -  Subjects with clinically significant laboratory value abnormalities at screening
             including but not limited to (note: exclusionary results may not be returned until
             after enrollment but should be confirmed by the time of the beginning of
             administration of study drug):

               1. Hemoglobin <5 g/dL

               2. Serum potassium <3.0 mEq/L

               3. Aspartate Aminotransferase or Alanine Aminotransferase ≥3.0 x ULN

        Part B:

        Same Eligibility Criteria except without diarrhea and is Cryptosporidium negative by qPCR.