Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of X842 in Human: A Single/Multiple Ascending Dose Study

NCT03105375 | Completed Early Phase 1 DMC

• 1 other identifier: CX842A2101
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess and analyze the safety, tolerability and PK/PD data following single ascending and multiple ascending doses of X842 in healthy subjects.

Conditions

Healthy Volunteers

Keywords

Potassium competitive acid blocker; X842; Gastroesophageal reflux disease; Esophagitis; Intragastric pH; Acid inhibition

Outcome Measures

Primary Outcomes (1)

• Occurrence and frequency of AEs, changes in laboratory parameters, vital signs and physical examination after single and multiple doses of X842. Summary statistics will be applied.

  Safety and tolerability will be assessed by occurrence and frequency of AEs, changes in laboratory parameters, vital signs and physical examination. The adverse event assessment will follow the recommendations and grading system of Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Summary statistics will be applied.

  Five weeks

Secondary Outcomes (3)

• Measurement of the PK profile (Cmax)

  Up to 48 hours after dosing

• Measurement of the PK profile (t1/2)

  Up to 48 hours after dosing

• Measurement of the PD profile (intragastric pH)

  Up to 24 hours after dosing

Study Arms (3)

Single ascending dose of X842

EXPERIMENTAL

Single ascending oral dose of X842 administered to subjects in cohorts. Cohorts are administered in sequence.

Drug: Single ascending dose of X842

Multiple ascending dose of X842

EXPERIMENTAL

Multiple ascending oral dose of X842 administered to subjects in cohorts. Cohorts are administered in sequence.

Drug: Multiple ascending dose of X842

Losec

ACTIVE COMPARATOR

Standard oral dose of omeprazole administered to subjects in one cohort.

Drug: Losec

Interventions

Single ascending dose of X842 DRUG

Each subject in a the same cohort will be assigned to the same single dose of X842. The subjects in the subsequent cohort will be assigned to a single dose of X842 based on safety and efficacy data generated from the previous cohort.

Also known as: X842

Single ascending dose of X842

Multiple ascending dose of X842 DRUG

Each subject in a the same cohort will be assigned to the same dose of X842 once daily for five days. The subjects in the subsequent cohort will be assigned to same dose of X842 once daily for five days based on safety and efficacy data generated from the previous cohort.

Also known as: X842

Multiple ascending dose of X842

Losec DRUG

Each subject in one cohort will be assigned to a standard dose of omeprazole once daily for five days.

Also known as: omeprazole

Losec

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give written informed consent for participation in the study.
• Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 and weight at least 50 kg and no more than 100 kg at screening.
• Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
• Male subjects must be willing to use condom and if they have a fertile partner, she must use contraceptive methods with a failure rate of \< 1% to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until three months after dosing of the IMP.
• Female subjects must be of non-childbearing potential (defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of amenorrhoea \[in questionable cases a blood sample with simultaneous follicle stimulation hormone 25-140 IE/L and estradiol \<200 pmol/L is confirmatory\]).

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• Present clinically significant psychiatric diagnosis, at discretion of the Investigator.
• Any clinically significant illness, medical/surgical procedure or trauma within four weeks of the first administration of investigational medical product.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past five years, regardless of whether there is evidence of local recurrence or metastases.
• History of any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs. The investigator is to be guided by evidence of any of the following: history of major gastrointestinal surgery such as gastrectomy, gastroenterostomy, bowel resection or Transjugular Intrahepatic Portosystemic Shunt (TIPS).
• History or presence of diagnosed and long-term treatment for GERD.
• Likelihood of having a gastric pH\>2 due to for example known autoimmune gastritis or known Helicobacter pylori gastritis.
• Known severe atrophic gastritis.
• Vitamin B-12 deficiency and/or chronic Vitamin B-12 substitution.
• Known malabsorption.
• Any planned major surgery within the duration of the study.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
• After 10 minutes of supine rest at the time of screening, any vital signs values outside the following ranges:
• Systolic BP 90 - 140 mm Hg
• Diastolic BP 50 - 90 mm Hg

Sponsors & Collaborators

• Cinclus Pharma AG: lead

Study Sites (1)

Clinical Trial Consultants

Uppsala, 75237, Sweden

Location

Related Publications (2)

• Andersson K, Carlsson E. Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases. Pharmacol Ther. 2005 Dec;108(3):294-307. doi: 10.1016/j.pharmthera.2005.05.005. Epub 2005 Jul 5.

  PMID: 16000224 BACKGROUND

• Hunt RH, Scarpignato C. Potassium-Competitive Acid Blockers (P-CABs): Are They Finally Ready for Prime Time in Acid-Related Disease? Clin Transl Gastroenterol. 2015 Oct 29;6(10):e119. doi: 10.1038/ctg.2015.39.

  PMID: 26513137 BACKGROUND

MeSH Terms

Conditions

Gastroesophageal Reflux; Esophagitis

Interventions

Omeprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Cornelia Lif-Tiberg, MD

  CTC Clinical Trial Consultants AB

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: SAD and MAD study

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: April 7, 2017
• Study Start: February 21, 2017
• Primary Completion: October 12, 2017
• Study Completion: October 12, 2017
• Last Updated: November 7, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)