Tiotropium Bromide Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease

NCT04780984 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: Neph-0002
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 2, Randomized, Partially-blinded, Parallel Group, Dose-ranging Study to Assess the Pharmacodynamics, Relative Bioavailability, and Safety of Three Doses of Tiotropium Bromide Inhalation Solution in Subjects with Chronic Obstructive Pulmonary Disease

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (1)

• Change in trough forced expiratory volume in 1 second (FEV1) compared with placebo

  The primary outcome measure will be the change in trough FEV1 from baseline at Visit 4 in the 8 μg, 16 μg, and 24 μg doses of tiotropium bromide inhalation solution treatment groups compared with that of placebo, will be evaluated by using a mixed model for repeated measure (MMRM) in the mITT population.

  22 days

Secondary Outcomes (2)

• Change in trough FEV1 compared with placebo and Sprivia Respimat

  22 days

• Change in forced vital capacity (FVC) compared with placebo and Sprivia Respimat

  22 days

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Placebo, 2mL

Drug: Placebo

Group 1 Tiotropium Bromide Inhalation Solution

EXPERIMENTAL

Treatment Dose (µg) Volume (mL) Concentration (µg/mL) 8 µg, 2.0 mL, 4 µg/mL

Drug: Tiotropium bromide inhalation solution

Group 2 Tiotropium Bromide Inhalation Solution

EXPERIMENTAL

Treatment Dose (µg) Volume (mL) Concentration (µg/mL) 16 µg, 2.0 mL, 8 µg/mL

Drug: Tiotropium bromide inhalation solution

Group 3 Tiotropium Bromide Inhalation Solution

EXPERIMENTAL

Treatment Dose (µg) Volume (mL) Concentration (µg/mL) 24 µg, 2.0 mL, 12 µg/mL

Drug: Tiotropium bromide inhalation solution

Spiriva Respimat

ACTIVE COMPARATOR

5 ug, 2 actuations, 2.5 µg/actuation

Drug: Tiotropium bromide inhalation solution

Interventions

Tiotropium bromide inhalation solution DRUG

Tiotropium bromide inhalation solution

Group 1 Tiotropium Bromide Inhalation Solution; Group 2 Tiotropium Bromide Inhalation Solution; Group 3 Tiotropium Bromide Inhalation Solution; Spiriva Respimat

Placebo DRUG

Placebo comparator

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and nonpregnant females, ages 40 to 80 years old, inclusive.
• On a stable COPD medication regimen defined as: no new medications for or changes to medications (dose/frequency) used to manage COPD within 60 days of screening.
• Willing and able to give informed consent and follow all study procedures and requirements.
• Body mass index \<35.
• Female subjects of child-bearing potential1 who are non-lactating, are using and agree tocontinue using an acceptable method of contraception for at least 4 weeks prior to first dose of study drug and until 12 weeks after last dose, and have a negative serum pregnancy test during screening. Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label, for example: abstinence from penile-vaginal intercourse; oral contraceptives, either combined or progestogen alone; injectable progestogen; implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device or intrauterine system; male partner sterilization at least 6 months prior to the female subject's screening visit, and this male is the sole partner for that subject (the information on the male partner's sterility can come from the site personnel's review of the subject's medical records or interview with the subject on her medical history); male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).
• Female subjects of childbearing potential who agree not to donate an ova during the study and for at least 30 days after the last dose of study drug.
• If male, agrees to use a condom with spermicide (note: no restrictions are required for a vasectomized male provided that his vasectomy was ≥ 4 months prior to the Screening Visit).
• Diagnosis of COPD, as defined by American Thoracic Society Global Initiative for Chronic Obstructive Lung Disease criteria
• Post-bronchodilator FEV1 ≥30% and ≤79%
• Post-bronchodilator FEV1/FVC ratio ≤70%
• Current or former smoker with a history of ≥ 10 pack-year history

You may not qualify if:

• Any condition that, in the opinion of the investigator, would interfere with the subject'sability to complete the study, would interfere with the interpretation of safety or efficacy, or would present an undue risk to the subject. In cases of uncertainty, the investigator may contact the medical monitor for clarification.
• Known respiratory disorders other than COPD that, in the opinion of the investigator, may present an unacceptable safety risk to a subject's study participation or could confound the interpretation of the study safety or efficacy results. Examples include, but are not limited to: alpha-1 antitrypsin deficiency, cystic fibrosis, significant asthma, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, pulmonary edema, or interstitial lung disease.
• Currently taking a non-selective beta blocker. Subjects who have been on a stable dose of a cardioselective beta blocker for at least 3 months prior to screening are not excluded (examples of cardioselective beta blockers are: metoprolol, atenolol, bisoprolol, and nebivolol). Topical beta blockers for ophthalmologic conditions are permitted.
• Uncontrolled diabetes defined as HbA1c \> 8.0%.
• Renal impairment defined as estimated glomerular filtration rate \<50 ml/min/1.73 m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation.
• Liver disease as defined as one or more of the following:
• AST or ALT \> 2 times the upper limit of normal (ULN).
• Total bilirubin \> 2 times the ULN (subjects with bilirubin elevation patterns consistent with Gilbert's disease are permitted).
• A history of or suspected, in the opinion of the investigator, bleeding disorder. Subjectson therapeutic anticoagulation are not excluded if the investigator believes they are appropriately anticoagulated.
• Eosinophil count \>600/mm3.
• History of a malignancy of any organ system (other than localized squamous or basal cell carcinoma of the skin) treated or untreated within the last 2 years prior to screening.
• Evidence or history of a clinically significant disease or abnormality, which, in the opinion of the investigator, would present and unacceptable safety risk to a subject's study participation or could confound the interpretation of the study efficacy or safety results. Examples of these conditions include, but are not limited to: NYHA Class II or higher congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, thyrotoxicosis, stroke, or cardiac dysrhythmia.
• Conditions which, in the opinion of the investigator, may contraindicate the use of an anticholinergic agent. Examples of these conditions may include, but are not limited to: paradoxical bronchospasm, narrow-angle glaucoma, prostatic hyperplasia, bladder neck obstruction, chronic constipation, or altered gastrointestinal motility.
• History of myasthenia gravis.
• Use of oral corticosteroids or oral antibiotics within 6 weeks prior to the Screening Visit.

Sponsors & Collaborators

• Nephron Pharmaceuticals Corporation: lead
• Rho, Inc.: collaborator

Study Sites (1)

Clinical Research of Rock Hill

Rock Hill, South Carolina, 29732, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: March 4, 2021
• Study Start: November 1, 2020
• Primary Completion: April 20, 2021
• Study Completion: April 26, 2021
• Last Updated: May 10, 2021

Record last verified: 2021-05

Locations

US (1)