Study to Compare Relative Bioavailability of 3 Indacaterol/Glycopyrronium Test Products and Reference Product (FORELLI)

Pharmacokinetic Formulation Feasibility Study to Compare Relative Bioavailability of 3 Indacaterol/Glycopyrronium Easyhaler Test Products and Reference Product Ultibro Breezhaler

This is a formulation feasibility study to to compare relative bioavailability of indacaterol and glycopyrronium after administration of single doses of 3 Easyhaler test products and Ultibro Breezhaler. The study treatments will be administered with concomitant oral charcoal to block absorption via gastrointestinal tract and to assess pulmonary absorption only.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Indacaterol/glycopyrronium

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • CRST Helsinki Oy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Healthy males and females
2. 18-60 years of age
3. Body mass index 19-30 kg/m2
4. Weight at least 50 kg
5. Written informed consent obtained

Main Exclusion Criteria:

1. Evidence of a clinically significant cardiovascular, renal, hepatic, haematological, GI, pulmonary, metabolic, endocrine, neurological or psychiatric disease
2. Any condition requiring regular concomitant treatment
3. Any clinically significant abnormal laboratory value, vital sign or physical finding that in the opinion of the investigator could interfere with the interpretation of study results or cause a health risk for the subject
4. Known hypersensitivity to indacaterol or glycopyrronium
5. Pregnant or lactating females and females of childbearing potential not using contraception of acceptable effectiveness
6. Blood donation or loss of significant amount of blood within 90 days prior to the first study treatment administration

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant A; Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant A in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses).	Drug: Indacaterol/glycopyrronium; In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.; Other Names: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant A with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant B with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant C with charcoal; Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal
Experimental: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant B; Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant B in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses).	Drug: Indacaterol/glycopyrronium; In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.; Other Names: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant A with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant B with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant C with charcoal; Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal
Experimental: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant C; Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant C in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses).	Drug: Indacaterol/glycopyrronium; In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.; Other Names: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant A with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant B with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant C with charcoal; Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal
Active Comparator: Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule; Each subject will receive 2 capsules of Ultibro® Breezhaler® (=Indacaterol/glycopyrronium) as a single dose in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses).	Drug: Indacaterol/glycopyrronium; In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.; Other Names: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant A with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant B with charcoal; Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant C with charcoal; Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak indacaterol and glycopyrronium concentration in plasma (Cmax)	Pharmacokinetic parameters of indacaterol and glycopyrronium	between 0-72 hours after dosing
Area under the concentration-time curve from time zero to 72 hours (AUC72)	Pharmacokinetic parameters of indacaterol and glycopyrronium	between 0-72 hours after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach peak indacaterol and glycopyrronium concentration in plasma (tmax)	Pharmacokinetic parameters of indacaterol and glycopyrronium	between 0-72 hours after dosing
Area under the concentration-time curve from time zero to 30 minutes (AUC30)	Pharmacokinetic parameters of indacaterol and glycopyrronium	between 0-30 minutes after dosing

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events	Up to 11 weeks

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Investigators: Study Director: Clinical Study Director, Orion Corporation, Orion Pharma

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): June 27, 2022
• Study Completion (Actual): June 27, 2022

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Protective Agents; Adjuvants, Anesthesia; Antidotes; Glycopyrrolate; Charcoal
• Other Study ID Numbers: 3131002

Drug and device information, study documents

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