Cardiodynamic ECG, GERD, Pharmacokinetics, Safety, and Tolerability
Conditions
Brief summary
This is a Phase I, single-center, double blind, placebo-controlled, parallel-group, randomized trial designed to evaluate the PK, cardiodynamic ECG effects, safety, and tolerability of single oral doses of linaprazan glurate. The trial will explore the PK properties of linaprazan glurate and linaprazan as well as the cardiodynamic ECG effects, safety, and tolerability after the administration of single doses: 300 mg and 600 mg in Part I of the trial, using formulation A of linaprazan glurate, as well as 150 mg, 275 mg, and up to 2 additional dose levels, using formulation C of linaprazan glurate to reach target linaprazan mean Cmax exposure (5222 nmol/L).
Interventions
Linaprazan glurate base formulation, 25 mg oral tablets (300 mg and 600 mg doses). Linaprazan glurate hydrochloride (HCl), 25 mg and 50 mg (as base) oral tablets (150 mg, 275 mg and up to 2 additional dose levels).
DRUGPlacebo
Single dose, oral tablets
Sponsors
Cinclus Pharma Holding AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Main inclusion Criteria: 1. Willing and able to give written informed consent for participation in the study. 2. Healthy male or female aged 18 to 65 years 3. Body mass index ≥18.5 and ≤35.0 kg/m2. 4. Prospective subjects, as well as their partners, must agree to contraception requirements Main
Exclusion criteria
1. Female subjects of childbearing potential unless they agree to use highly effective methods of contraception (failure rate of \<1%) from 2 weeks prior to dosing until the end-of-study visit. 2. Male subjects with a partner of childbearing potential, unless they agree to use method of contraception from 2 weeks prior to dosing until the end-of-study visit.History of or current clinically significant disease as defined in the protocol 3. History of or current clinically significant disease as defined in the protocol. 4. History of GERD, significant acid reflux. 5. Subjects who are pregnant, currently breastfeeding, or intend to become pregnant (female subjects) or father a child (male subjects) during the course of the study (i.e., from screening to end of study visit).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (AUCinf) | Up to 24 hours | To assess the Area under the plasma concentration vs. time curve (AUC) from time 0 to infinity (AUCinf) |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (AUClast) | Up to 24 hours | To assess the AUC from time 0 to the last measurable concentration (AUClast) |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (Cmax) | Up to 24 hours | To assess the Maximum plasma concentration (Cmax) |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (T1/2) | Up to 24 hours | To assess the Terminal elimination half-life (T1/2) |
| Measurement of Cardiodynamic ECG (QTcF) | Up to 24 hours | To assess the change from baseline in QTcF |
| Measurement of Cardiodynamic ECG (heart rate) | Up to 24 hours | To assess the change from baseline in heart rate |
| Measurement of Cardiodynamic ECG (PR interval) | Up to 24 hours | To assess the change from baseline in PR interval |
| Measurement of Cardiodynamic ECG (QRS interval) | Up to 24 hours | To assess the change from baseline in QRS interval |
| Measurement of Cardiodynamic ECG (placebo-corrected QTcF) | Up to 24 hours | To assess the change from baseline in placebo-corrected QTcF |
| Measurement of Cardiodynamic ECG (placebo-corrected heart rate) | Up to 24 hours | To assess the change from baseline in placebo-corrected heart rate |
| Measurement of Cardiodynamic ECG (placebo-corrected PR interval) | Up to 24 hours | To assess the change from baseline in placebo-corrected PR interval |
| Measurement of Cardiodynamic ECG (placebo-corrected QRS interval) | Up to 24 hours | To assess the change from baseline in placebo-corrected QRS interval |
| Measurement of Cardiodynamic ECG (categorical outliers) | Up to 24 hours | Number of categorical outliers for ECG parameters (QTcF, HR, PR interval, QRS interval) |
| Measurement of Cardiodynamic ECG (changes of T-wave) | Up to 24 hours | Frequency of treatment emergent changes of T-wave abnormalities |
| Measurement of Cardiodynamic ECG (changes of U-wave) | Up to 24 hours | Frequency of treatment emergent changes of U-wave abnormalities |
Countries
Sweden
Contacts
CONTACTSophie Leyman, MD
CONTACTKajsa Larsson, MD, PhD
PRINCIPAL_INVESTIGATORErik Rein-Hedin, MD
CTC Clinical Trial Consultants AB
Outcome results
None listed