LCZ696 regional absorption pharmacoscintigraphic study
Research type
Research Study
Full title
A pharmacoscintigraphic clinical study to assess the regional absorption of LCZ696 in healthy volunteers
IRAS ID
226028
Contact name
Howard N.E. Stevens
Contact email
Sponsor organisation
Drug Delivery International
Eudract number
2017-003924-63
Duration of Study in the UK
0 years, 2 months, 19 days
Research summary
This study will investigate four new prototype LCZ696 tablets, developed by Drug Delivery International (DDi), each containing valsartan and sacubitril as the active ingredients. The combination of valsartan and sacubitril is currently available commercially as Entresto film-coated tablets (marketed by Novartis).\n\nEntresto tablets are taken by patients twice a day, therefore the new LCZ696 tablets are being developed as modified release formulations to enable once daily dosing. Dosing once per day will require the drug to release over a prolonged period of time, and the aim of this study will be to understand the absorption characteristics of the drug complex at different regions in the gastrointestinal tract.\n\nThis is a four-period, four-treatment, open-label crossover pharmacoscintigraphic study, recruiting up to 16 healthy male volunteers. Subjects will receive one treatment at each visit. Four prototype tablets will be tested throughout the study: \n\nV1. Enteric-coated LCZ696 tablet (to release in the upper small intestine)\nV2. Enteric-coated delayed-release LCZ696 tablet (3 hr delay following gastric emptying, to release in the terminal ileum)\nV3. Enteric-coated delayed-release LCZ696 tablet (5 hr delay following gastric emptying, to release in the colon)\nV4. Entresto commercial tablet + delayed release LCZ696 tablet (7-8 hr delay following dosing, to release in the colon)\n\nEach tablet contains 48 mg sacubitril and 51 mg valsartan.\n\nA radiolabel containing 4 MBq technetium-99m (99m-Tc) will be added to each prototype LCZ696 tablet to allow sequential scintigraphic images to be taken using a gamma camera following dosing. The commercially available Entresto tablet will not be radiolabelled, but will act to simulate a biphasic (two phase e.g. immediate release and delayed release) formulation when administered with the delayed-release prototype. Blood samples will also be drawn to allow the measurement of drug levels in the bloodstream.
REC name
North East - York Research Ethics Committee
REC reference
17/NE/0296
Date of REC Opinion
12 Oct 2017
REC opinion
Favourable Opinion