Phase 1 Study Assessing the Safety and Tolerability of CTX-4430 in Cystic Fibrosis Patients

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CTX-4430 When Administered Orally to Cystic Fibrosis Patients for Fifteen Days

The purpose of this study is to assess the safety and tolerability of multiple oral doses of CTX-4430 when administered to cystic fibrosis (CF) patients once-daily (QD) for 15 days.This study will include two dose levels. For each dose level, blood samples will be collected for exploratory PK and PD assay validation. In addition, sputum will be collected for exploratory biomarker analysis. Following multiple dose administration, pulmonary function and exploratory lung clearance index (LCI) measurements will be taken.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: CTX-4430; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G31 2ER
    • Glasgow Clinical Research Facility
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9QZ
      • The Medicinces Evaluation Unit
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 6AD
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult male or female, 18 to 55 years of age (inclusive) at the time of screening.
2. Confirmed diagnosis of CF based on the following: positive sweat chloride or sodium value ≥ 60 mEq/L, and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype or a diagnosis of CF made by a specialist in this condition.
3. In the judgment of the Principal Investigator (PI), the patient is medically stable with no change in symptoms, medication, or with clinical laboratory results that in PI opinion are compatible with the diagnosis of either CF or a complication thereof and are judged acceptable for inclusion.
4. Body mass index (BMI) ≥ 17.0 (kg/m2).
5. Non-tobacco/nicotine-containing product user for a minimum of 6 months prior to the first study drug administration.
6. Forced Expiratory Volume (FEV1) of >50% and <90% of predicted at screening.
7. Must agree to use adequate method of contraception.

Exclusion Criteria:

1. Patient has displayed any significant clinical/laboratory/radiological/spirometric sign of unstable or unexpectedly deteriorating respiratory disease within 30 days prior to the first study drug administration.
2. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease that depart from the patient's usual baseline level of health as a patient with CF.
3. Has a history of lung transplantation.
4. History or presence of alcoholism or drug abuse within 2 years prior to the first study drug administration.
5. Personal or family history of prolonged QT syndrome; or a QTc interval >430 msec (males) or >450 msec (females) using Bazett's formula (QTcB) or deemed clinically significant by the PI.
6. Sitting blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg, unless deemed clinically insignificant by the PI.
7. Pulse is higher than 100 b.p.m or lower than 50 b.p.m. unless deemed clinically insignificant by the PI.
8. Failure to satisfy the PI of fitness to participate for any other reason.
9. In the judgment of the PI, clinically significant hemoptysis (>30 cc per episode) within the last 180 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Once daily oral capsule containing 50 or 100 mg of CTX-4430	Drug: CTX-4430; Ascending repeat doses of CTX-4430 will be administered orally, once-daily, to patients in 2 cohorts on days 1-15.
Placebo Comparator: Placebo; Once daily oral capsule containing mannitol, visibly identical to CTX-4430 capsules	Drug: Placebo; Repeat doses of placebo will be administered orally, once-daily, to patients in 2 cohorts on days 1-15; Other Names: Mannitol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the safety and tolerability of multiple oral doses of CTX-4430 when administered to cystic fibrosis (CF) patients once-daily (QD)	Changes in clinical signs and symptoms of safety data that include physical examinations, ECGs, vital signs, pulse oximetry, pulmonary function (spirometry), clinical laboratory results, and adverse events which will be summarized descriptively and reported in tabular form.	15 days

Collaborators and Investigators

• Sponsor: Celtaxsys, Inc.
• Collaborators: Celerion
• Investigators: Principal Investigator: J Stuart Elborn, MD, FRCP, Queen's University, Belfast

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: September 6, 2013
• First Submitted That Met QC Criteria: September 13, 2013
• First Posted (Estimate): September 18, 2013

Study Record Updates

• Last Update Posted (Estimate): March 6, 2015
• Last Update Submitted That Met QC Criteria: March 4, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: CTX-4430-CF-001