Safety study reveals new antibiotic for C. difficile infections is well tolerated in healthy volunteers

An experimental antibiotic for Clostridium difficile infections developed with support from the Wellcome Trust has successfully completed a phase I clinical trial and is well tolerated by healthy volunteers.

SMT 19969 is a new antibiotic compound being developed by Oxford-based drug discovery company Summit Plc. as a targeted therapy for C. difficile infections.

The phase I clinical trial was a double-blind, placebo-controlled study involving a total of 56 healthy male volunteers to determine a safe dosage range for SMT 19969 and identify any possible side-effects. After a single dosing phase, the volunteers received twice-daily doses of SMT 19969 for ten days. The study showed that SMT 19969 is well tolerated at and above the expected therapeutic dose with no adverse side-effects.

The study also measured the impact of the experimental drug on the harmless strains of bacteria that are normally found in the gut. Early results reveal that it is highly sparing of these strains and only bacteria from the same family as C. difficile, the Clostridia, were reduced to levels below the limit of detection. These top-level results provide an encouraging indication of the potential of SMT 19969 as a targeted therapy for C. difficile infections.

"The positive safety and tolerability of SMT 19969 in this human phase I trial is a major success," said Glyn Edwards, CEO of Summit.

"The results of the gut flora analysis are particularly encouraging because they indicate that SMT 19969 could target C. difficile without undermining the natural balance of gut flora. This reinforces our belief that SMT 19969 can become a breakthrough treatment for this life-threatening disease."

Professor Mark Wilcox, Consultant and Clinical Director of Microbiology and Pathology at the Leeds Teaching Hospitals NHS Trust, and the Health Protection Agency's leader on C. difficile infection in England, added: "There is evidence that maintaining a healthy gut flora is important in warding off disease recurrence in C. difficile infections. It is very encouraging that in humans SMT 19969 is highly sparing of gut flora, meaning that it offers promise as an urgently needed treatment for this serious disease."

C. difficile is the most important cause of hospital-acquired infections. Infection often occurs when patients are treated with antibiotics for a separate illness, which disrupts the balance of harmless bacteria in the gut. This enables C. difficile bacteria to take over and cause disease, resulting in severe diarrhoea, nausea and vomiting.

The only treatment options for C. difficile infections are broad-spectrum antibiotics that also damage the natural gut bacteria populations. However, they sometimes do not kill all of the C. difficile bacteria, and antibiotic-resistant strains are on the increase.

Relapsing infections are common in up to 30 per cent of patients, and it is these repeat episodes that are the most dangerous; severe cases can prove fatal. New treatments that can selectively target C. difficile bacteria are therefore urgently needed.

Dr Ted Bianco, Acting Director and Director of Technology Transfer at the Wellcome Trust, said: "As well as the threat to patient lives, hospital infections place a significant burden on our health system by increasing costs and lengths of hospital stays. As the UK's Chief Medical Officer calls for global action to tackle growing antibiotic resistance, the results of this first safety trial bring us a step closer towards a better targeted therapy for C. difficile infections, for which existing antibiotics are often ineffective."

Preclinical development of SMT 19969 was supported by a Seeding Drug Discovery Award, and Summit has received an additional Translation Award from the Wellcome Trust to continue its development through phase II clinical trials.