Bioequivalence Between Albuterol Sulfate Inhalation Aerosol 108mcg Per Actuation and Proair HFA (Albuterol Sulfate) Inhalation Aerosol 90 mcg Per Actuation in Healthy Volunteers Under Fasting Conditions

• ClinicalTrials.gov Identifier: NCT04803734
• Recruitment Status: Active, not recruiting
• First Posted: March 18, 2021
• Last Update Posted: June 2, 2021
• Sponsor: Intech Biopharm Ltd.
• Information provided by (Responsible Party): Intech Biopharm Ltd.

Study Description

Brief Summary:

The objective of this study is to evaluate the bioequivalence between two formulations of MDI, eq. to albuterol 90mcg/puff in healthy volunteers under fasting conditions.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Albuterol Sulfate inhalation aerosol 108mcg per actuation; Drug: Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Randomized, Single-dose, Open-label, Two-way Crossover Pivotal Study to Assess the Bioequivalence Between Albuterol Sulfate Inhalation Aerosol 108mcg Per Actuation (MDI, eq. to Albuterol 90mcg/Puff) and Proair HFA (Albuterol Sulfate) Inhalation Aerosol 90 mcg Per Actuation (MDI, eq. to Albuterol 90mcg/Puff) in Healthy Volunteers Under Fasting Conditions
• Actual Study Start Date: March 28, 2021
• Actual Primary Completion Date: May 10, 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Test; Albuterol Sulfate inhalation aerosol	Drug: Albuterol Sulfate inhalation aerosol 108mcg per actuation; MDI, 2 puffs, single dose, fasting; Other Name: Albuterol 90mcg/puff
Active Comparator: Reference; Proair HFA (albuterol sulfate) Inhalation Aerosol	Drug: Proair HFA (albuterol sulfate) Inhalation Aerosol 90 mcg per actuation; MDI, 2 puffs, single dose, fasting; Other Name: Albuterol 90mcg/puff

Outcome Measures

Primary Outcome Measures :

1. Cmax [ Time Frame: 0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ]
   Pharmacokinetics of Albuterol Sulfate by Assessment of Observed Maximum Plasma Concentration (Cmax)
2. AUC(0-t) [ Time Frame: 0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ]
   Pharmacokinetics of Albuterol Sulfate by Assessment of Observed Maximum Plasma Concentration (AUC(0-t))
3. AUC(0-inf) [ Time Frame: 0 hour (pre-dose), as well as at 2, 5, 10, 15, 20, 30, 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ]
   Pharmacokinetics of Albuterol Sulfate by Assessment of Observed Maximum Plasma Concentration (AUC(0-inf))

Secondary Outcome Measures :

1. Tmax [ Time Frame: 0-24 hours ]
   Other Pharmacokinetics of Albuterol Sulfate by Assessment of Time to Maximum Plasma Concentration (Tmax)
2. T1/2 [ Time Frame: 0-24 hours ]
   Other Pharmacokinetics of Albuterol Sulfate by Assessment of Terminal Elimination Half-life (T1/2)
3. kel(λ) [ Time Frame: 0-24 hours ]
   Other Pharmacokinetics of Albuterol Sulfate by Assessment of Terminal Climination Rate Constant (kel(λ))
4. MRT [ Time Frame: 0-24 hours ]
   Other Pharmacokinetics of Albuterol Sulfate by Assessment of Mean residence time (MRT)
5. Adverse Events [ Time Frame: Through study completion, an average of 16 days ]
   The number and type of adverse events will be reported from Day 1 of period 1 through Day 2 of period 2 including a 14 day washout period between periods (total time is approximately 16 days)

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy male and female volunteers, aged 20-60, inclusive.
2. BMI of 18.0-30.0 kg/m², inclusive. The body weight should be over 50 kg, inclusive. (BMI will be calculated as weight in kilogram [kg]/height in meters² [m²]).
3. Healthy or Non Clinical Significant, according to the medical history, ECG, chest X-ray and physical examination as determined by the Principal Investigator/Sub-Investigator.
4. Systolic blood pressure between 90-139 mmHg, inclusive, and diastolic blood pressure between 50-90 mmHg, inclusive, and pulse rate between 50-100 bpm, inclusive and temperature between 35.0-37.4℃.
5. Screening laboratory values within reference range or NCS as determined by the Principal Investigator/Sub-Investigator.
6. Ability to comprehend and be informed of the nature of the study, as assessed by clinical staff. Capable of giving written informed consent prior to receiving any study medication. Must be able to communicate effectively with clinical staff.
7. Willing to fast for at least 14 hours and to consume standard meals.
8. Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.
9. Agree not to have a tattoo, body piercing, or other any invasive procedure and blood donation until the end of the study.
10. Never-smokers; or former smokers who have smoked ≥ 100 cigarettes in their lifetime and have not consumed any tobacco or tobacco containing products for at least 12 months prior to screening.
11. Subjects who are non-asthmatic, defined as no clinical history of asthma, allergy or atopy.
12. Able to perform special breathing using nebulizer correctly as per the required standard.

13. Subjects must fulfill at least one of the following:

    • Be surgically sterile for a minimum of 6 months;
    • Post-menopausal for a minimum of 1 year;
    • Agree to avoid pregnancy and use medically acceptable method of contraception from screening day until 30 days after the study ends (last study procedure).

Exclusion Criteria:

1. Known history or presence of any clinically significant hepatic (e.g. active liver disease, hepatic impairment), renal/genitourinary (e.g. renal impairment), gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine (e.g. hypothyroidism), immunological, musculoskeletal (e.g. myopathy, rhabdomyolysis), neurological, psychiatric, dermatological, hematological disease, or any other medical conditions, unless determined as not clinically significant by the Principal Investigator/Sub-Investigator.
2. Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the Principal Investigator/Sub-Investigator.
3. Presence of any significant physical or organ abnormality as determined by the Principal Investigator/Sub-Investigator.
4. A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, tetrahydrocannabinol), breath alcohol test. Positive pregnancy test for female subjects.

5. Known history or presence of:

   • Alcohol abuse within one year prior to first drug administration;
   • Drug abuse or dependence;
   • Hypersensitivity or idiosyncratic reaction to albuterol, its excipients, and/or related substances;
   • Allergy to standardized meal provided by site and/or presence of any dietary restrictions;
6. Intolerance to and/or difficulty in blood sampling through venipuncture.
7. Abnormal diet patterns (for any reason) during the 4 weeks preceding the study, including fasting, high protein diets etc.
8. Except for screening procedures, blood donation that results in blood loss of not more than 250 ml in the past 2 months prior to first dosing; blood loss of more than 250 ml within 3 months prior to first dosing.
9. Donation of plasma by plasmapheresis within 7 days prior to first drug administration.
10. Individuals who receives an investigational drug from 2 months prior to first drug administration.
11. Consumption of products containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hours before dosing and products containing grapefruit and/or pomelo (shown to inhibit cytochrome P450 [CYP] 3A4 activity) within 10 days prior to first drug administration.
12. Use of any medication, including oral multivitamins, herbal and/or dietary supplements within 30 days prior to first drug administration (except topical agents without systemic absorption as determined by the Principal Investigator/Sub-Investigator).
13. Females taking oral or transdermal hormonal contraceptives within 30 days prior to first drug administration.
14. Females having used implanted, injected, intravaginal, or intrauterine hormonal contraceptive within 6 months prior to first drug administration.
15. Individuals having undergone any major surgery within 6 months prior to the start of the study, unless deemed otherwise by Principal Investigator/Sub-Investigator.
16. Using tobacco products, nicotine products (patches, gum etc.) within 6 months prior to first drug administration.
17. Lactating women.

Contacts and Locations

Locations

Taiwan

Clinical Pharmacology Unit,Mackay Memorial Hospital

New Taipei City, Taiwan

Sponsors and Collaborators

Intech Biopharm Ltd.

More Information

• Responsible Party: Intech Biopharm Ltd.
• ClinicalTrials.gov Identifier: NCT04803734
• Other Study ID Numbers: TW20-4502
• First Posted: March 18, 2021
• Last Update Posted: June 2, 2021
• Last Verified: May 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Respiratory Aspiration; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action