This is a single-centre, blinded, randomized, placebo controlled, dose escalation study. Up to 9 healthy male volunteers will participate in the study. This study is designed to investigate the use of delayed release tablets for colonic delivery of Brilacidin.
Brilacidin is a fully synthetic, non-peptidic, host defense protein mimetic, and has been shown to demonstrate anti-inflammatory and antibacterial activities. Two prototype tablets have been developed to contain 50 mg or 100 mg of Brilacidin. Matching placebo tablets have also been developed. In this Phase 1 study, the delayed release prototype tablets will be tested to confirm efficient and specific target release of Brilacidin in the colon and to assess the safety, tolerability and the pharmacokinetics of Brilacidin administered directly to the colon. Three subjects will be enrolled into each cohort of the study. Each subject will receive one treatment at one Assessment Visit. In each cohort, two subjects will receive a Brilacidin containing dose, and one subject will receive placebo. Cohort 1: 50 mg Brilacidin or Placebo; Cohort 2: 100 mg Brilacidin or Placebo; Cohort 3: 200 mg Brilacidin (as 2 x 100 mg Brilacidin tablets) or 2 x Placebo. Each treatment (drug and placebo) will be radiolabelled with technetium-99m (99mTc). The radiopharmaceutical, 99mTc-DTPA, does not enter the systemic circulation and is routinely used for investigations of this type. In Cohort 1 and 2 each tablet, including placebo, will be radiolabelled to contain approximately 4 MBq 99mTc-DTPA at time of dosing. In Cohort 3 each individual tablet, active or placebo, will be radiolabelled with 2 MBq 99mTc-DTPA to give a total dose of 4 MBq per treatment. Each tablet will be taken orally with 200 mL room temperature water with subjects in the fasted state. The gastrointestinal transit and release behavior of the tablets will be studied using gamma scintigraphy. Blood samples will be taken at pre-defined times to allow pharmacokinetic (PK) evaluation of drug absorption with respect to time and location of tablet release.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
9
Brilacidin
Placebo
4Mq technetium-99m (99mTc), complexed with diethylenetriaminepentaacetic acid (DTPA) which prevents absorption of the radioisotope from the gastrointestinal tract
BDD Pharma Ltd
Glasgow, Scotland, United Kingdom
Site of release of radiolabel
Site of release of radiolabel determined by a qualified assessor based on gamma scintigraphy images
Time frame: To 14 hours post-dose
Time to release of radiolabel
Site of release of radiolabel determined by a qualified assessor based on gamma scintigraphy images
Time frame: To 14 hours post-dose
To visualise radiolabel dispersion within the colon
To visualise the disintegration and dispersion of delayed release tablets from gamma scintigraphy images of the colon
Time frame: To 14 hours post-dose
Cmax
Maximum Plasma Concentration
Time frame: To 24 hours post-dose
Tmax
Time of Maximum Plasma Concentration
Time frame: To 24 hours post-dose
Tlag
Lag Time
Time frame: To 24 hours post-dose
AUClast
Area Under the Curve from time 0 to 24 hours
Time frame: To 24 hours post-dose
AUC0-inf
Area Under the Curve from time 0 to infinity
Time frame: To 24 hours post-dose
K
Terminal First Order Rate constant
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Time frame: To 24 hours post-dose
t1/2
Half Life
Time frame: To 24 hours post-dose
Adverse Events
Number of Participants With Treatment-Emergent Adverse Events
Time frame: 14 days