First in man healthy volunteer safety study. Investigational drug is being developed for treatment of C. difficile infections. Infections and Infestations Clostridium difficile infection
Conditions
Interventions
A partially blind, placebo controlled, randomised study conducted in 2 parts:
Part 1: Comprises of an ascending single oral dose sequential group study (Groups A to D and F) and a food effect evaluat
Sponsors
Summit Corporation PLC (UK)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Subjects will be required to satisfy the following criteria at the screening visit unless otherwise stated: 1. Subjects will be healthy males of any ethnic origin between 18 and 55 years of age. 2. Body Mass Index (BMI) between 18.0 and 32.0 kg/m2 inclusive; and a total body weight within the range of 50 kg to 100 kg. 3. Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if they satisfy the following criteria at the screening visit unless otherwise stated: 1. Male subjects who are not willing, or whose partners are not willing, to use appropriate contraception (such as a condom with spermicidal foam/gel/film/cream/suppository), or are not willing to refrain from donating sperm from the time of the first dose until 3 months after the final dosing occasion. 2. Subjects who have received any prescribed systemic or topical medication within 14 days of the first dose administration unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety. 3. Subjects who have used any non-prescribed systemic or topical medication (including vitamins and dietary supplements) within 7 days of the first dose administration unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety. Herbal supplements must be discontinued at least 28 days prior to the first dose of trial medication. Exceptions: Paracetamol may be used at doses of 140 mmHg or diastolic BP >90 mmHg at screening), resting hypotension (systolic BP <90 mmHg or diastolic BP <50 mmHg at screening) or bradycardia (heart rate <40 bpm at screening). 8. Subjects who consume more than 28 units of alcohol per week within 6 months of screening or who have a significant history of alcoholism or drug/chemical abuse as determined by the Investigator (1 unit of alcohol equals ½ pint [285 mL] of beer or lager, 1 glass [125 mL] of wine, or 1/6 gill [25 mL] of spirits) 9. Subjects with a positive urine drug screen or alcohol breath test result at screening or first admission. 10. Subjects who smoke in excess of 15 cigarettes/day. 11. Subjects with, or with a history of, any clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or allergic disease (including significant drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) as determined by the Investigator. 12. Subjects who have had a clinically significant illness within 4 weeks of the start of dose administration as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the safety and tolerability of ascending single and multiple oral doses of SMT19969 in healthy male subjects. 1. Ongoing daily monitoring for adverse events through questioning by investigator and spontaneous reporting by subjects 2. Assessment of vital signs (supine blood pressure, supine pulse rate and oral body temperature) at 1, 2, 4, 8, 24, 48 and 72 hours post-dose in Part 1 and in Part 2 on Day 1; 2, 4, 8 and 12 hours post-am dose, Days 2, 4, 6 and 8; Pre-am dose and 2 h post am dose and on Day 10; Pre-dose, 2, 4, 8, 12, 24 and 48 hours postdose 3. 12-lead ECG assessment at 2, 6, 24, 48 and 72 hours post-dose in Part 1 and in Part 2 on Day 1; 2 and 8 hours post-am dose, on Days 3 and 7; 2 h post am dose and on Day 10; Pre-dose, 2, 8, 24 and 48 hours post-dose 4. Blood and urine samples will be collected for clinical laboratory evaluations (standard panel of serum biochemistry, urinalysis, haematology and serology) 72 hours post-dose in Part 1 and in Part 2 on Days 1 and 7; Pre-am dose and Day 10; Pre-dose, and 48 hours post-dose 5. Assessment of faecal samples for the presence of Faecal Occult Blood, as voided from 48 to 72 h post-dose in Part 1 and in Part 2 on the first sample voided on Days 4, 9 and 11 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the single and multiple oral dose PK of SMT19969 in healthy male subjects. 1.1. SMT19969 will be quantified in blood samples taken in Part 1 at Pre-dose, 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose and in Part 2 on Day 1; Pre-am dose, 1, 2, 4, 8 and 12 hours post am dose, Days 2 to 9; Pre-am dose and on Day 10: Pre-dose, 1, 2, 4, 8, 12, 24, and 48 hours post-dose 2. To assess the effect of food on the systemic exposure of SMT19969 in healthy male subjects. 2.1. Subjects in Group E will take part in two treatment periods (TP1 and TP2) at least 6 days apart. In TP1 subjects will receive a single 1,000mg oral dose of SMT19969 under fasted conditions and in TP2 will receive a single 1,000mg oral dose of SMT19969 following a high fat meal. 3. To assess the effect of multiple oral doses of SMT19969 on gut flora (via assessment of faecal samples) in healthy male subjects. 3.1. The first faecal sample voided in Part 2 on days -1, 4 and 9 will be pooled and assessed for gut flora composition by quantitative culture of the following bacteria: Bacteroides, Bifidiobacteria, Lactobacilli, total Clostridia, total anaerobes, lactose-fermenting enterobacteriaceae and total aerobes. 4. To determine concentrations of SMT19969 in faecal samples and potentially conduct exploratory work in plasma and faecal samples using Orbitrap analysis (a technique used to look at potential metabolites, degradants and/or biomarkers). 4.1. SMT19969 will be quantified in faecal samples in Part 1 as voided from 0 to 72 h post-dose and in Part 2 on pooled samples voided over a 24 hour period on days 5 and 10. 4.2. Selected faecal and plasma samples may be retained for further analysis of metabolites. | — |
Countries
United Kingdom
Outcome results
None listed