A Trial to Assess the Bioequivalence of Generic Tiotropium Bromide Inhalation Powder and Reference Product in Healthy Adult Participants Under Fasting Conditions (Pilot)

A Single-Center, Open-Label, Randomized, Single-Dose, Two-Period, Two-Sequence, Crossover Trial to Assess the Bioequivalence of Test Product Tiotropium Bromide Inhalation Powder (Strength: 18 mcg) and Reference Product (Spiriva®Handihaler®, Strength: 18 mcg) in Healthy Adult Participants Under Fasting Conditions (Pilot)

Primary Objective: To evaluate the pharmacokinetics of Tiotropium Bromide Inhalation Powder (Strength:18 mcg; manufactured by Chia Tai Tianqing Pharmaceutical Group Co. Ltd) and reference products Tiotropium Bromide Inhalation Powder (Spiriva®, Handihaler®, Strength: 18mcg, manufactured by Boehringer Ingelheim Pharmaceuticals, Inc) by oral inhalation of single dose in healthy participants under fasting conditions.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Tiotropium Bromide Inhalation Powder; Drug: Spiriva HandiHaler

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan (Zhengzhou) Zhonghui Cardiovascular Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to give signed Informed Consent Form before the trial, and fully understand the trial content, process and possible adverse drug reactions (ADRs);
• Able to complete the trial in compliance with the protocol;
• Participants (including males) willing to adopt effective contraceptive methods and with no pregnancy plan from 14 days before screening to 3 months after the last scheduled visit;
• Males and females between 18 and 55 years old (included);
• At least 50 kg for males, 45 kg for females, with a Body Mass Index (BMI) = Weight/Height2 (kg/m2) between 19.0-26.0 kg/m2 (included);
• No history of cardiac, hepatic, renal, ophthalmology and otorhinolaryngology, respiratory system, urogenital system, digestive tract, nervous system, mental and metabolic disorders, etc.

Exclusion Criteria:

• Take ≥ 5 cigarettes per day on average within 3 months before screening, or not able to quit smoking during the trial, or urine nicotine test is positive;
• Be allergic to tiotropium, atropine or its derivatives (e.g., ipratropium, oxitropium) or any excipient of tiotropium bromide inhalation sprays; or allergic constitution (be allergic to two or more drugs, food and pollen allergy); or with specific allergy history (asthma, urticaria, eczema, etc.);
• A history of alcohol abuse (alcohol consumption of more than 14 units per week: 1 unit of alcohol = 285 mL beer, or 25 mL spirits, or 100 mL wine);
• Blood donation or massive blood loss (≥ 400 mL) within 3 months before the initial administration; Or any blood donation plan from screening until 1 month after the last administration;
• Participants who have an acute upper respiratory tract infection within 2 weeks prior to receiving investigational product;
• History of any clinically significant diseases or any other diseases that could interfere with the study results. Including but not limited to the circulatory system, gastrointestinal system, urinary system (such as history of prostate hypertrophy, bladder neck obstruction, uroschesis, etc.), respiratory system (such as acute onset of chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary hypertension, pulmonary edema, pulmonary interstitial disease, bronchospastic pulmonary disease, bronchial asthma, etc.), ophthalmology (such as: glaucoma, etc.), nervous system, immune system, endocrine system, malignant tumor, mental and metabolic abnormalities; or with history of nasopharyngitis, throat ulcers, edema, or history of throat, tracheal/bronchial and lung surgery in the past;
• History of sicca syndrome or habitual constipation;
• Function test: the forced expiratory volume in one second measured value / the forced expiratory volume in one second predicted value ≤80% or the forced expiratory volume in one second / forced vital capacity ≤80%;
• Any prescription medication within 14 days before the initial administration;
• Any over-the-counter (OTC) medication or Chinese herbal medicine or health supplementary within 7 days before the initial administration;
• Consumption of any special diets (such as grapefruit), or strenuous exercise engagement, or other factors affecting drug absorption, distribution, metabolism and excretion within 7 days before the initial administration;
• Participation in other drug clinical trials within 3 months before the initial administration;
• Any clinically significant abnormality findings, as judged by a clinical physician, such as physical examination, vital signs, electrocardiogram, chest X-ray examination and laboratory tests;
• Positive results of hepatitis B surface antigen, hepatitis C antibody, and HIV antibody or syphilis;
• Consumption of chocolate or any food/beverage containing caffeine or rich in xanthine within 48 hours before the initial administration;
• Consumption of any products containing alcohol within 48 hours before the initial administration, or a positive result of the alcohol breath test;
• A positive result of the drug abuse test, or a history of drug abuse in the past 5 years, or intake of any narcotic drugs within 3 months prior to the trial;
• A positive result of the pregnancy test, or in lactation during screening or the test period for female participants;
• History of fainting needle or blood;
• Not tolerable on venipuncture, or a history of difficulty in venous blood collection;
• Special requirements and unable to follow the unified diet, or intolerance to lactose or galactose;
• Unable to participate in this trial for participants' own reasons;
• Participants who cannot control of powder inhaler oral inhalation correctly after training;
• Other conditions in which participants are not suitable for the trial determined by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Product Tiotropium Bromide Inhalation Powder (Strength: 18 mcg); The subjects randomly received single oral inhalation dose of Tiotropium bromide inhaling powder generic product.	Drug: Tiotropium Bromide Inhalation Powder; It's a generic product of Spiriva HandiHaler.
Active Comparator: Reference Product (Spiriva®Handihaler®, Strength: 18 mcg); The subjects randomly received single oral inhalation dose of the reference listed drug (RLD) Spiriva®Handihaler®.	Drug: Spiriva HandiHaler; Tiotropium Bromide Inhalation Powder RLD, which binds to M3 receptors, and blocks the action of acetylcholine to relieve spasm of bronchial smooth muscle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak concentration (Cmax)	Maximum plasma drug concentration	Pre-dose and 1 2, 3, 4, 5 6, 7, 8, 10, 15, 20, 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168, 216 hours post-dose
Area under the plasma concentration versus time curve (AUC) 0-t	plasma concentration-time curve from zero to the time of the last measurable time point t.	Pre-dose and 1 2, 3, 4, 5 6, 7, 8, 10, 15, 20, 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168, 216 hours post-dose
Area under the plasma concentration versus time curve (AUC) 0-∞	area under the plasma concentration-time curve from zero to infinity	Pre-dose and 1 2, 3, 4, 5 6, 7, 8, 10, 15, 20, 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168, 216 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to maximum plasma concentration (Tmax)	The time to maximum plasma concentration (observed)	Pre-dose and 1 2, 3, 4, 5 6, 7, 8, 10, 15, 20, 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168, 216 hours post-dose
The elimination half-life (t1/2)	Elimination half-life of plasma concentration	Pre-dose and 1 2, 3, 4, 5 6, 7, 8, 10, 15, 20, 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168, 216 hours post-dose
Terminal elimination rate constant (Kel)	Terminal elimination rate constant	Pre-dose and 1 2, 3, 4, 5 6, 7, 8, 10, 15, 20, 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168, 216 hours post-dose

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2024
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: March 17, 2024
• First Submitted That Met QC Criteria: March 17, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: STXA-BE-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No