Severe Clostridium difficile Infection (CDI) Infections and Infestations Severe Clostridium difficile Infection (CDI)
Conditions
Interventions
Interventions as of 30/09/2016:
The study is in two cohorts. Cohort 1 (single doses) will be conducted in up to 10 subjects (1 sub-cohort of 2 subjects and one sub-cohort of 8 subjects
Sponsors
MicroPharm Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female subjects between 18 and 70 years of age. At least 2 subjects in each cohort should be > 60 years of age. (added 30/09/2016) 2. Female subjects of non-child bearing potential with negative pregnancy test at screening visit (to be confirmed prior to first dose) 3. Male subject willing to use two effective methods of contraception (unless anatomically sterile or abstaining as preferred and usual lifestyle) 4. Body Mass Index between 18.5 and 30 5. No clinically significant abnormal serum biochemistry, haematology and urine levels measured within 28 days of the first dose 6. Negative results for urinary drugs of abuse screen, determined within 28 days of the first dose (a positive alcohol test may be repeated at the discretion of the Investigator) 7. Negative HIV and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results 8. No clinically significant abnormalities in vital signs (blood pressure, pulse, respiration rate and oral temperature) determined within 28 days of the first dose 9. No clinically significant abnormalities in 12-lead ECG determined within 28 days of the first dose 10. Available to complete the study (including all follow-up visits) 11. Subject must satisfy a medical examiner about their fitness to participate in the study 12. Subject must provide written informed consent to participate
Exclusion criteria
Exclusion criteria: 1. Receipt of regular prescription and / or OTC medication within 28 days of the first dose that may have an impact on the safety and objectives of the study (at the Investigator’s discretion) 2. Subjects with any clinically significant disease including but not limited to cardiovascular, respiratory, metabolic, immunologic, hepatic, renal, endocrinal, neurologic, skin or psychiatric disease 3. Subject with a current or past history of any psychological or psychiatric disorders 4. Evidence of gastrointestinal, renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction 5. Subjects with allergy/ hypersensitivity to any medication including marketed, unmarketed or OTC medications. Any clinically significant findings at planned site of infusion, including dark skin, tattoos or veins not suitable for venepuncture. 6. A clinically significant allergic disease (excluding non-active seasonal allergy) 7. A clinically significant history of drug or alcohol abuse in past 3 years 8. Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function) 9. Participation in a clinical study or receipt of treatment with any ovine antibodies or other ovine serum constituents 10. Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the previous 30 days (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study) 11. Donation of 450 mL or more blood within the previous 3 months 12. Vaccination within the previous 3 months which may have an impact on the safety or objectives of the study (at the Investigator’s discretion) To be confirmed at Baseline / Prior to First Dose: 1. Development of any exclusion criteria since the Screening Visit 2. Receipt of any medication since the Screening Visit that may have an impact on the safety and objectives of the study (at the Investigator’s discretion)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort 1: 1. Adverse Events (AEs) and concomitant medication check are monitored continuously throughout the study 2. 12 lead ECGs pre-dose, day 1 (at 2, 4, 8 and 12 hours), and days 2, 8, 15, 22, 29 3. Vital signs (compared with pre-dose values) including supine blood pressure, heart rate, respiratory rate and temperature are measured pre-dose, day 1 (at 2, 4, 8 and 12 hours), and days 2, 8, 15, 22, 29 4. Local tolerability assessment (degree of erythema with or without induration, vesicles, bullae, pustules, erosion or ulceration at the injection site) is measured pre- and immediately post-dose, day 1 (at 15 min, 30 min, 1, 2, 8 and 12 hours), and days 2, 3, 6, 8, 15, 22, 29 5. Laboratory safety tests on haematology (haemoglobin, haematocrit, mean cell volume, mean cell haemoglobin concentration, red blood cells, while blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets), biochemistry ( total protein, albumin, total bilirubin, alanine transaminase, aspartate transaminase, gamma glutamyl transferase, glucose, sodium, potassium, bicarbonate, creatinine and urea) and urinalysis (protein, glucose, specific gravity, ketones, urobilinogen, bilirubin, pH and blood) are measured on days 1, 3, 8, 15, 22 and 29 Cohort 2: 1. 12 lead ECGs are completed on days 1, 4 and 7 (pre-dose, 2h, 4h, 8h, 12h), and days 2 5, 8, 15, 22 and 29 2. Vital signs (as above) are measured on days, 1, 4 and 7 (pre-dose, 2h, 4h, 8h, 12h), and days 2, 5, 8, 10, 12, 15, 22 and 29 3. Local tolerability (as above) are measured on days 1, 4 and 7 (pre- and immediately post-dose, 15 min, 30 min, 1h, 2h, 8h, 12h), and days 2, 5, 8, 10, 12, 15, 22 and 29 4. Laboratory safety tests (as above) are measured on days 1, 2, 5, 8, 15, 22 and 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Cohort 1: 1. Drug concentration measurements for pharmacokinetic determinations, determined by measuring (by immunoassay) the presence of ovine immunoglobulins in the subjects’ serum are measured pre-dose, immediately on completion of drug or placebo infusion, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 7 d, 14 d, 28 d. 2. Immunogenicity –Immunoassay to determine the development of human antibodies directed against ovine immunoglobulins are measured pre-dose, and on days 8, 15, 22, and 29 Cohort 2: 1. Drug concentration measurements for pharmacokinetic determinations, determined by measuring (by immunoassay) the presence of ovine immunoglobulins in the subjects’ serum are measured for days 1, 4 and 5 - Pre-dose, immediately upon completion of the drug/placebo infusion, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h. In addition, for day 7: 3 d, 5 d, 8d, 15 d, and 22d. 28 d. 2. Immunogenicity –Immunoassay to determine the development of human antibodies directed against ovine immunoglobulins are measured pre-dose, and on days 8, 15, 22, and 29 | — |
Countries
United Kingdom
Outcome results
None listed