Celgosivir or Modipafant as Treatment for Adult Participants With Uncomplicated Dengue Fever in Singapore

Launched by SINGAPORE GENERAL HOSPITAL · Oct 5, 2015

Keywords

ClinConnect Summary

This trial is a single centre, double-blind, double-dummy, placebo-controlled parallel-group, dose ranging study in adult participants with uncomplicated dengue fever. The study will be conducted in two parts:

In Part 1, 72 otherwise healthy participants (18 participants per group, assuming up to 2 dropouts per group) with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be randomised to receive treatment with placebo, celgosivir or modipafant. Participants will be randomised in parallel to one of Cohorts 1 to 4:

* Cohort 1: Placebo Q6Hours for 5 days
* Cohort 2: M...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male or female, aged 21-65 years;
• • 2. Acute febrile illness with two or more manifestations (headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, or leucopoenia) and occurrence at the same location and time as other confirmed cases of dengue fever;
• • 3. Fever (\> 37.5°C) or history of fever at screening
• • 4. \< 48 hours of fever history
• • 5. Positive NS1 strip assay or reverse-transcriptase polymerase chain reaction (RT-PCR).
• • 6. Able and willing to give written informed consent; and,
• • 7. Willing to be an inpatient from Study Screening to Study Day 5 and to return to hospital on study Days 14 and 28.
• • 8. Willing to keep a study diary from Study Day 5 to Day 14.
• Exclusion Criteria:
• 1. Clinical signs and symptoms for severe dengue, such as:
• • Severe abdominal pain;
• • Persistent vomiting;
• • CS fluid accumulation;
• • Mucosal bleeding;
• • Altered mental state;
• • Liver enlargement \> 2 cm;
• • Systolic blood pressure \< 90 mmHg; and
• • Pulse pressure \< 20 mmHg.
• 2. A person with any of the following laboratory values:
• • Haematocrit \>52% males; \>46% females;
• • Aspartate or alanine aminotransferase (AST or ALT) \> 1000 U/L;
• • Room air oxygen saturation \< 95%;
• • Absolute neutrophil count \< 1500/µL;
• • Platelet count \< 80,000/mm3;
• • Creatinine \> 165 µmol/L males; \> 130 µmol/L females;
• • Haemoglobin \< 13.0 g/dL males; \< 11.0 g/dL females;
• • Total bilirubin \> 24 µmol/L; and
• • Serum CPK \> 600 U/L.
• • 3. History of or presently active intestinal disorders such as peptic ulcers, intestinal ulcers, intestinal obstructions, intestinal hernias, ulcerative colitis, malabsorption syndrome, celiac disease, Roemheld's syndrome (gastroesophageal regurgitation disease) or Crohn's disease;
• • 4. Severe diarrhoea (grade 2 or higher according to NIH clinical trial guidelines);
• • 5. Current usage of any anticoagulant drugs including, but not limited to, aspirin, warfarin or clopidogrel;
• • 6. Any other CS acute illness within seven days prior to first study drug administration;
• • 7. History of adverse reactions to celgosivir, castanospermine, modipafant or formulation excipients or history of severe drug or food allergies;
• • 8. Exposure to any new investigational drug within 30 days prior to the study drug administration;
• • 9. CS abnormal physical examination unrelated to dengue infection, chest X-ray or 12-lead ECG at screening such as QTc prolongation (\> 450 msec);
• • 10. Women of child bearing potential (WOCBP) who are pregnant, breast feeding or unwilling to avoid pregnancy by the use of highly effective contraception (\<1% failure rate per year) including oral and subcutaneous implantable hormonal contraceptives, condoms, diaphragm, or intra-uterine system (IUS), during the period that the experimental drug is administered. Prospective WOCBP must have a negative pregnancy test (point of care).
• • 11. Male participants unwilling to comply with the contraceptive requirements of the study as detailed in Section 4.7 (i.e. abstinence, effective barrier contraception during the study and for 65 days after the last dose of study drug).
• • 12. Current significant medical condition or illness including cardiac arrhythmias, cardiomyopathy or other cardiac disease, asthma or other respiratory disease, diabetes mellitus, renal or hepatic impairment, thyroid disease, Parkinson's disease, epilepsy or history of unexplained blackouts, immunocompromised state including known HIV infection, or any other illness that the Investigator considers should exclude the patient, especially those that require continuation of other medications likely to have an interaction with the study drug.
• • 13. Any condition that would render the informed consent invalid, or limit the ability of the participant to comply with the study requirements.
• • 14. Any condition that, in the opinion of the Investigator, would complicate or compromise the study or well-being of the participant.