Safety, Tolerability and Pharmacokinetics of PUR1900 (Itraconazole Powder) in Healthy Volunteers and Adults With Asthma

NCT03479411 | Completed Phase 1

• 1 other identifier: 601-0013
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

Phase 1, 3-part study to assess safety, tolerability and PK of single and multiple doses of itraconazole administered as a dry powder for inhalation (PUR1900) in healthy subjects (parts 1 and 2) and a 2-period crossover study of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and an oral solution (Sporanox) in adults with mild to moderate, stable asthma (part 3)

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0

  Safety and tolerability will be assessed by evaluating the number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28

Secondary Outcomes (7)

• Area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf) of single dose of itraconazole

  Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28

• Time of the maximum measured serum concentration (Tmax) of single dose of itraconazole

  Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28

• Area under the serum concentration vs time curve within the dosing interval (AUCtau) of single dose of itraconazole

  Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28

• Apparent first-order terminal elimination half-life (t1/2 ) of single dose of itraconazole

  Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28

• Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the serum concentration vs time curve (Kel) of single dose of itraconazole

  Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28

Other Outcomes (2)

• Maximum Concentration [Cmax] of itraconazole and hydroxyitraconazole in sputum

  Part 3: baseline through 28 days

• Area under the Curve [AUC] of itraconazole and hydroxyitraconazole in sputum

  Part 3: baseline through 28 days

Study Arms (3)

Part 1 single ascending dose

EXPERIMENTAL

Intervention: drug Itraconzaole powder: single dose of 5mg, 10mg or 25 mg Other name: PUR1900

Drug: Itraconazole Powder

Part 2 multiple ascending dose

EXPERIMENTAL

Intervention: drug Itraconzaole powder: 10 mg or 20 mg daily for 14 days Other name: PUR1900

Drug: Itraconazole Powder

Part 3 2-period crossover single dose

ACTIVE COMPARATOR

Intervention: drug Itraconzaole powder: 20 mg single dose and Itraconzaole oral solution 200 mg single dose Other names: PUR1900, Sporanox

Drug: Itraconazole Powder; Drug: Itraconazole 200 mg

Interventions

Itraconazole Powder DRUG

Itraconazole administered as a dry powder for inhalation (PUR1900)

Also known as: PUR1900

Part 1 single ascending dose; Part 2 multiple ascending dose; Part 3 2-period crossover single dose

Itraconazole 200 mg DRUG

Sporanox® Oral Solution

Also known as: Sporanox®

Part 3 2-period crossover single dose

Eligibility Criteria

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

You may qualify if:

• Part 1 (SAD) and Part 2 (MAD):
• Healthy males or non-pregnant, non-lactating healthy females.
• Age 18 to 60 years
• Screening forced expiratory volume in 1 sec (FEV1) ≥80% of the predicted value
• Screening FEV1/forced vital capacity (FVC) \>0.70.
• Able to demonstrate the correct inhalation technique for use of delivery device during the study.
• Part 3 (Asthmatic Subjects):
• Males or non-pregnant, non-lactating females with a physician-confirmed diagnosis of asthma for at least 3 months. Asthma must be assessed by investigator as being stable for at least 4 weeks prior to screening.
• Age 18 to 60 years
• Subject is being treated with either inhaled corticosteroids (ICS) or inhaled corticosteroids plus long-acting beta-agonists (ICS/LABA). Only GINA STEP 2 and 3 patients will be enrolled.
• Pre-bronchodilator, clinic measured, FEV1 ≥70% of predicted normal at screening
• Able to perform the required spirometric testing.
• Able to produce a sputum sample of a quality required for drug concentration assessments (a single repeat is permitted).

You may not qualify if:

• Subjects who have received any IMP in a clinical research study within the previous 3 months prior to dosing on this study
• Subjects who have previously received IMP in this study. Subjects who have participated in Part 1 are not permitted to participate in Part 2 or Part 3.
• History of any drug or alcohol abuse in the past 2 years prior to screening.
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study (all female subjects must have a negative pregnancy test at screening). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause (will be re-assessed at admission/pre-dose).
• Positive drugs of abuse test result at screening or admission
• Subjects with congestive heart failure or a history of congestive heart failure
• History of severe cough or bronchospasm upon inhalation of any dry powder inhalation product
• Subjects who are taking or have taken any herbal remedies or CYP3A4 inducers in the 28 days prior to the first IMP administration
• Upper respiratory tract infection (excluding otitis media), fever, acute or chronic cough within 14 days of the first IMP administration, or lower respiratory tract infection within the last 3 months prior to IMP administration
• Recent (last 4 weeks prior to IMP administration) clinically significant bacterial, viral or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals or antifungals; topical treatments, other than antifungals, are allowed.

Sponsors & Collaborators

• Pulmatrix Inc.: lead

Study Sites (2)

Medicines Evaluation Unit

Manchester, United Kingdom

Location

Quotient Sciences

Nottingham, United Kingdom

Location

Related Publications (1)

• Bergagnini-Kolev M, Kane K, Templeton IE, Curran AK. Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data. AAPS J. 2023 Jun 21;25(4):62. doi: 10.1208/s12248-023-00828-z.

  PMID: 37344751 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Itraconazole

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• James Roach, MD

  Pulmatrix Inc.

  STUDY DIRECTOR

Study Design

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

Model Details: The study has 3 parts: 1) Single Ascending Dose Escalation and 2) Multiple Ascending Dose Escalation to be conducted in Normal Healthy Volunteers and 3) A two-period crossover study of single doses of PUR1900 and Sporanox in Adults with Asthma

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: March 27, 2018
• Study Start: February 9, 2018
• Primary Completion: June 28, 2018
• Study Completion: June 28, 2018
• Last Updated: July 27, 2018

Record last verified: 2018-07

Locations

GB (2)