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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Linaprazan glurate | Experimental | Oral administration as a single dose of 300 mg, 600 mg, 150 mg, 275 mg, and up to 2 additional dose levels. |
|
| Placebo | Placebo Comparator | Oral administration as a singel dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linaprazan glurate | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (AUCinf) | To assess the Area under the plasma concentration vs. time curve (AUC) from time 0 to infinity (AUCinf) | Up to 24 hours |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (AUClast) | To assess the AUC from time 0 to the last measurable concentration (AUClast) | Up to 24 hours |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (Cmax) | To assess the Maximum plasma concentration (Cmax) | Up to 24 hours |
| Measurement of pharmacokinetic profile of linprazan glurate and linaprazan (T1/2) | To assess the Terminal elimination half-life (T1/2) | Up to 24 hours |
| Measurement of Cardiodynamic ECG (QTcF) | To assess the change from baseline in QTcF | Up to 24 hours |
| Measurement of Cardiodynamic ECG (heart rate) | To assess the change from baseline in heart rate | Up to 24 hours |
| Measurement of Cardiodynamic ECG (PR interval) | To assess the change from baseline in PR interval | Up to 24 hours |
| Measurement of Cardiodynamic ECG (QRS interval) |
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Main inclusion Criteria:
Main exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sophie Leyman, MD | Contact | +32 470214020 | sophie.leyman@cincluspharma.com | |
| Kajsa Larsson, MD, PhD | Contact | +46 70 675 01 28 | kajsa.larsson@cincluspharma.com |
| Name | Affiliation | Role |
|---|---|---|
| Erik Rein-Hedin, MD | CTC Clinical Trial Consultants AB | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CTC Clinical Trial Consultants AB | Recruiting | Uppsala | SE-75237 | Sweden |
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| ID | Term |
|---|---|
| D005764 | Gastroesophageal Reflux |
| ID | Term |
|---|---|
| D015154 | Esophageal Motility Disorders |
| D003680 | Deglutition Disorders |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
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|
| Placebo | Drug | Single dose, oral tablets |
|
To assess the change from baseline in QRS interval |
| Up to 24 hours |
| Measurement of Cardiodynamic ECG (placebo-corrected QTcF) | To assess the change from baseline in placebo-corrected QTcF | Up to 24 hours |
| Measurement of Cardiodynamic ECG (placebo-corrected heart rate) | To assess the change from baseline in placebo-corrected heart rate | Up to 24 hours |
| Measurement of Cardiodynamic ECG (placebo-corrected PR interval) | To assess the change from baseline in placebo-corrected PR interval | Up to 24 hours |
| Measurement of Cardiodynamic ECG (placebo-corrected QRS interval) | To assess the change from baseline in placebo-corrected QRS interval | Up to 24 hours |
| Measurement of Cardiodynamic ECG (categorical outliers) | Number of categorical outliers for ECG parameters (QTcF, HR, PR interval, QRS interval) | Up to 24 hours |
| Measurement of Cardiodynamic ECG (changes of T-wave) | Frequency of treatment emergent changes of T-wave abnormalities | Up to 24 hours |
| Measurement of Cardiodynamic ECG (changes of U-wave) | Frequency of treatment emergent changes of U-wave abnormalities | Up to 24 hours |
| D004066 | Digestive System Diseases |