A Study to Assess the Effect of AZD5634 on Mucociliary Clearance, Safety, Tolerability and Pharmacokinetic Parameters in Patients With Cystic Fibrosis

NCT02950805 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: D6600C00002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

This study will assess the effect of inhaled AZD5634 on Mucociliary clearance (MCC) in patients with Cystic fibrosis (CF) after single-dose administration.

Conditions

Pulmonary/Respiratory Diseases

Keywords

AZD5634; Mucociliary Clearance; Safety; Tolerability; Pharmacokinetic; Cystic Fibrosis; Cross-Over Study

Outcome Measures

Primary Outcomes (1)

• Percentage of average whole lung particle clearance between 0 and 60 minutes after administration of aerosolized radiolabelled particles

  Assessment of the average whole lung clearance between 0 and 60 minutes after administration of single inhaled dose of aerosolized radiolabelled particles (colloids) of AZD5634, (%MCC 0--60, whole) in subjects with cystic fibrosis (CF).

  0 to 60 minutes

Secondary Outcomes (35)

• Percentage of average central clearance between 0 and 60 minutes after administration of aerosolized radiolabelled particles

  0 to 60 minutes

• Percentage of average peripheral clearance between 0 and 60 minutes after administration of aerosolized radiolabelled particles

  0 to 60 minutes

• Percentage of average tracheobronchial clearance between 0 and 60 minutes after administration of aerosolized radiolabelled particles

  0 to 60 minutes

• Percentage of particle clearance at 6-hour

  6 hours

• Percentage of average whole lung cough clearance between 60 minutes and 90 minutes after administration of aerosolized radiolabelled particles

  60 minutes to 90 minutes

Study Arms (2)

Placebo + AZD5634

EXPERIMENTAL

Subjects were administered single dose of placebo in period 1 and AZD5634 in period 2.

Drug: Placebo; Drug: AZD5634

AZD5634 + Placebo

EXPERIMENTAL

Subjects were administered single dose of AZD5634 in period 1 and placebo in period 2.

Drug: Placebo; Drug: AZD5634

Interventions

Placebo DRUG

Subjects will receive a placebo in either period 1 or period 2 by inhalation.

AZD5634 + Placebo; Placebo + AZD5634

AZD5634 DRUG

Subjects will receive a single tentative dose of 625 μg of AZD5634 in either period 1 or period 2 by inhalation.

AZD5634 + Placebo; Placebo + AZD5634

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated written informed consent prior to any study-specific procedures.
• Male or female patients aged 18-60 years old inclusive.
• Diagnosed of CF at Screening as evidenced in medical records by one of the following criteria:
• sweat chloride ≥ 60 mmol/L
• presence of 2 mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene.
• Chronic sinopulmonary disease or pancreatic insufficiency.
• FEV1measurement at Screening ≥ 40% of the predicted normal value of age, height, gender, and race.
• Stable CF regimen for at least 2 months before Screening.
• Body mass index (BMI) between 15-30 kg/m2 inclusive.
• Female patients are not pregnant and do not plan to become pregnant during the study, are not lactating, or are of non-childbearing potential. Females of childbearing potential must provide a negative serum pregnancy test and have a date of last menstruation consistent with non-pregnancy, negative urine pregnancy tests at each visit, and must be using at least one highly effective method of contraception.
• Ability of the patient to correctly perform the inhalation procedure after training during the Screening Visit.

You may not qualify if:

• Had a pulmonary exacerbation requiring change in antibiotics and/or hospitalization within 28 days before the first dose of Investigational product.
• History of lung transplant or any other transplantation.
• Currently being treated with ivacaftor monotherapy at Screening or received ivacaftor monotherapy within 30 days before Screening.
• History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the Investigator, to drugs in a similar class to AZD5634.
• History or presence of hepatic cirrhosis.
• Creatinine clearance \<60 mL/min/m2 using the Cockroft-Gault Equation.
• Liver function test results \>2x upper limit of normal (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], gamma-glutamyl transpeptidase \[GGT\], or bilirubin)
• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
• Received treatment with the following medications within the 3 weeks before Screening: strong or moderate Cytochrome P450 (CYP) 3A inhibitors, as classified by the Food and Drug Administration (FDA).
• Likely to require treatment during the study with drugs not permitted by the study protocol.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results.
• Serum potassium levels are outside the normal range (3.5-5.1 mmol/L).
• Serum sodium levels \<135 mmol/L.
• Abnormal vital signs, after 5 minutes rest, at Screening or Visit 2 (seated or supine; position should be consistent for a given patient at both visits), defined as any of the following:
• Systolic blood pressure (B.P) \< 90 or ≥ 150 mmHg

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (3)

Research Site

Birmingham, Alabama, 35294-1785, United States

Location

Research Site

Baltimore, Maryland, 21205, United States

Location

Research Site

Chapel Hill, North Carolina, 27517, United States

Location

Related Publications (1)

• Kristensson C, Astrand A, Donaldson S, Goldwater R, Abdulai R, Patel N, Gardiner P, Tehler U, Mercier AK, Olsson M, Ersdal E, Maenpaa J, Bramer T, Malmgren A, Bennett W, Keen C. AZD5634, an inhaled ENaC inhibitor, in healthy subjects and patients with cystic fibrosis. J Cyst Fibros. 2022 Jul;21(4):684-690. doi: 10.1016/j.jcf.2022.02.010. Epub 2022 Feb 26.

  PMID: 35227647 DERIVED

MeSH Terms

Conditions

Respiratory Tract Diseases; Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: November 1, 2016
• Study Start: May 30, 2017
• Primary Completion: April 12, 2018
• Study Completion: April 12, 2018
• Last Updated: July 13, 2018

Record last verified: 2018-07

Locations

US (3)