Date: 2015-06-23
Type of information: Results
phase: 1
Announcement: results
Company: Zealand Pharma (Denmark)
Product: ZP4207
Action
mechanism: glucagon analog.
Disease: severe hypoglycemia in Type 1 and Type 2 diabetes patients
Therapeutic area: Metabolic diseases
Country: Germany
Trial
details: The trial is a randomized, double-blind First in Human trial to evaluate the safety and tolerability of ZP4207 in healthy volunteers (HV) and in insulin-induced hypoglycemic T1D (type 1 diabetes) subjects as compared to native glucagon. The trial includes two parts. Part 1 includes dose escalation of ZP4207 in cohorts of 8 subjects. In each cohort, subjects will be randomized 3:1 to receive either a single ascending dose of ZP4207 (6 subjects) or a single fixed dose (SD) of native glucagon (2 subjects). The doses will be administered s.c. in 4-5 cohorts and i.m. in 3 cohorts. Part 2 includes two sequence groups of 10 hypoglycemic T1D subjects. The subjects will be treated with fixed single doses of ZP4207 and native glucagon s.c. in a sequential cross-over design in a randomized treatment order. (NCT02367053)
Latest
news: * On June 26, 2015, Zealand Pharma announced results from a clinical Phase I trial with a single-dose version of its novel, stable glucagon analogue, ZP4207. ZP4207, invented and wholly-owned by Zealand, is suited for liquid formulation and has in preclinical studies shown promising potential as a more convenient ready-to-use rescue pen for the treatment of severe hypoglycemia. Zealand initiated the ZP4207 single-dose Phase I trial in November 2014 as a two-part study to evaluate safety and tolerability in both healthy volunteers and Type 1 diabetes patients. The enrollment and treatment of 64 healthy volunteers and 20 patients with Type 1 diabetes was completed ahead of schedule. Based on the results from the trial, Zealand will now progress the development of ZP4207 for severe hypoglycemia towards the next clinical phases. The first-in-man Phase I trial comprised two parts. In Part 1, Zealand enrolled 64 healthy volunteers who were treated with single-ascending doses of ZP4207 primarily to evaluate safety and tolerability and secondarily to evaluate various pharmacokinetic and pharmacodynamic measurements compared to a marketed glucagon hypoglycemia rescue treatment. Results showed that ZP4207 was safe and well tolerated across all doses evaluated (0.01 mg to 2.0 mg per subject). Furthermore, blood glucose levels were increased as expected across a broad dose range. In Part 2 of the trial, the same endpoints were evaluated for a selected single dose of ZP4207 in 20 patients with Type 1 diabetes. The patients were challenged with insulin into hypoglycemia before treatment with ZP4207 to get an indication of the efficacy of ZP4207 to release glucose stores and increase blood glucose levels in a cross-over design with a marketed glucagon rescue treatment as direct active comparator. In parallel with the development of ZP4207 as a single-dose rescue treatment, Zealand is also evaluating a multiple-dose version of ZP4207 in a clinical Phase IB trial for the treatment of mild to moderate hypoglycemia including its potential use in a dual-hormone artificial pancreas pump. The ongoing development activities, including chronic toxicology studies, are supported by a $ 1.8 million grant from the Helmsley Charitable Trust. The enrolment into the Phase Ib trial has now been completed, and results are expected in H2 2015. * On November 17, 2014, Zealand Pharma announced that the company has dosed the first human subjects in a clinical Phase I trial with ZP4207, its novel stable glucagon analogue. The objectives of the trial are to evaluate the safety and human efficacy of ZP4207 as a novel approach to offer better and more convenient treatment of severe hypoglycemia. In preclinical studies, ZP4207 has demonstrated a strong stability profile and a good solubility, supporting the potential use of this glucagon analogue in a liquid dosage form as a ready-to-use rescue pen. Data from these studies suggest further that ZP4207 is comparable to native glucagon in its effect on releasing glucose stores into the blood stream to restore blood sugar levels, while being suitable for long term storage. Zealand currently retains all rights to ZP4207. In the first part of the Phase I clinical trial, conducted at a selected diabetes centre in Germany, Zealand expects to enrol up to 64 healthy volunteers who will be treated with single-ascending doses of ZP4207. The trial objectives are primarily to evaluate safety and tolerability and secondarily to evaluate various pharmacokinetic and pharmacodynamic measurements, as compared to native glucagon. In a second part of the trial, the same endpoints will be evaluated in 20 patients with Type 1 diabetes, who will be made hypoglycemic before treatment to get an indication of the efficacy of ZP4207 to release glucose stores and increase blood sugar levels in a cross-over design with native glucagon as active comparator. Zealand expects to complete the Phase I trial in H1 2015 with results available mid 2015. The clinical development of ZP4207 as a better and more convenient treatment of severe episodes of hypoglycemia has the potential to follow an expedited plan, which could lead to first regulatory filing of this Zealand therapeutic as soon as early 2018.
