A Clinical Study to Evaluate Z7200 (Budesonide/Formoterol) Pharmacokinetics Profile in Healthy Volunteers

NCT02237508 | Completed Phase 1 Results

• 2 other identifiers: Z7200J022014-002081-69
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective was: \- to assess the bioequivalence of a single dose (two inhalations) of the test product compared to the reference product, with and without charcoal blockade. The secondary objectives were:

• to assess the pharmacokinetic profile of budesonide and formoterol in plasma after a single dose (two inhalations) of the test product and the reference product, with and without charcoal blockade.
• to assess the safety and tolerability of the test product and the reference product, with and without charcoal blockade.

Conditions

Asthma

Outcome Measures

Primary Outcomes (4)

• AUC0-t of Budesonide With and Without Charcoal Blockade

  Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

• AUC0-t of Formoterol With and Without Charcoal Blockade

  Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

• Cmax of Budesonide With and Without Charcoal Blockade

  Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

• Cmax of Formoterol With and Without Charcoal Blockade

  Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Secondary Outcomes (11)

• AUC0-30 of Budesonide With and Without Charcoal Blockade.

  0-30 min (0, 2, 5, 10, 15, 20, and 30 min)

• AUC0-30 of Formoterol With and Without Charcoal Blockade.

  0-30 min (0, 2, 5, 10, 15, 20, and 30 min)

• AUC0-∞ of Budesonide With and Without Charcoal Blockade

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

• AUC0-∞ of Formoterol With and Without Charcoal Blockade

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

• Tmax for Budesonide With and Without Charcoal Blockade

  0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Study Arms (10)

A-B1-B2-C-D

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 days followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

B1-C-A-D-B2

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

C-D-B1-B2-A

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

D-B2-C-A-B1

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

B2-A-D-B1-C

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

D-C-B2-B1-A

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

B2-D-A-C-B1

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

A-B2-B1-D-C

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

B1-A-C-B2-D

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

C-B1-D-A-B2

EXPERIMENTAL

Subjects were dosed on Day 1 of each treatment period with one of the following five treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B2: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period of a minimum of 5 day followed treatment periods 1 to 4. Treatment B1 and B2 denote Symbicort without oral activated charcoal administered in two different period, designated as Symbicort 1 and Symbicort 2.

Drug: Z7200 without oral activated charcoal; Drug: Symbicort Turbohaler without oral activated charcoal; Drug: Z7200 with oral activated charcoal; Drug: Symbicort Turbohaler with oral activated charcoal

Interventions

Z7200 without oral activated charcoal DRUG

160 ug budesonide and 4.5 ug formoterol fumarate dihydrate, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A).

Also known as: budesonide/formoterol

A-B1-B2-C-D; A-B2-B1-D-C; B1-A-C-B2-D; B1-C-A-D-B2; B2-A-D-B1-C; B2-D-A-C-B1; C-B1-D-A-B2; C-D-B1-B2-A; D-B2-C-A-B1; D-C-B2-B1-A

Symbicort Turbohaler without oral activated charcoal DRUG

320 ug budesonide and 9 ug formoterol fumarate dihydrate, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2).

Also known as: budesonide/formoterol

A-B1-B2-C-D; A-B2-B1-D-C; B1-A-C-B2-D; B1-C-A-D-B2; B2-A-D-B1-C; B2-D-A-C-B1; C-B1-D-A-B2; C-D-B1-B2-A; D-B2-C-A-B1; D-C-B2-B1-A

Z7200 with oral activated charcoal DRUG

160 ug budesonide and 4.5 ug formoterol fumarate dihydrate, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C).

Also known as: budesonide/formoterol with coadministration of charcoal

A-B1-B2-C-D; A-B2-B1-D-C; B1-A-C-B2-D; B1-C-A-D-B2; B2-A-D-B1-C; B2-D-A-C-B1; C-B1-D-A-B2; C-D-B1-B2-A; D-B2-C-A-B1; D-C-B2-B1-A

Symbicort Turbohaler with oral activated charcoal DRUG

320 ug budesonide and 9 ug formoterol fumarate dihydrate, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation from a Symbicort Turbohaler, with charcoal blockade (Treatment D).

Also known as: budesonide/formoterol with coadministration of charcoal

A-B1-B2-C-D; A-B2-B1-D-C; B1-A-C-B2-D; B1-C-A-D-B2; B2-A-D-B1-C; B2-D-A-C-B1; C-B1-D-A-B2; C-D-B1-B2-A; D-B2-C-A-B1; D-C-B2-B1-A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female 18 to 45 years of age.
• If female, is currently not pregnant/breast feeding/ or attempting to become pregnant has a negative serum pregnancy test, or is of non-childbearing potential or is of child-bearing potential, willing to commit to using a consistent and acceptable method of birth control or is of child-bearing potential and not sexually active
• Body mass index (BMI) of 18.5 to 29.9 kg/m² inclusive and a body weight ≥50 kg.

You may not qualify if:

• FEV1 value less than 80% of the predicted value and FEV1/FVC ratio \<0.7.
• History or current evidence of a clinically significant disease or disorder capable of altering the absorption, metabolism, distribution or elimination of drugs.
• History or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, haematological, neuropsychological, endocrine, gastrointestinal or pulmonary.
• Presence of glaucoma, cataracts, ocular herpes simplex, malignancy, regardless of the clinical significance or current stability of the disease.
• History or presence of silent infections, including positive tests for HIV1, HIV2, Hepatitis B and Hepatitis C.
• Bacterial or viral infection of the upper respiratory tract (including the common cold and flu), sinus, or middle ear within 2 weeks of dosing.
• Lower respiratory tract infection/pneumonia within the past 3 months.
• Presence of any disease or condition or regular concomitant treatment (including vitamins and herbal products) known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Screening haemoglobin value of less than 1g/dL above the ULN (or 10g/L)
• History of recurrent vasovagal collapses.
• History of anaphylactic/anaphylactoid reactions.
• History of seizures including febrile seizures excluding childhood febrile convulsions.
• Unable to demonstrate proper inhalation techniques involved in using the delivery devices at screening.
• Exposure to any investigational drug within 90 days of the Screening Visit.
• Known or suspected hypersensitivity or idiosyncratic reaction to any steroid, any β2 agonist,or to lactose monohydrate, leucine or Tween 80.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (1)

Quotient Clinical Ltd

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

Charcoal; Budesonide, Formoterol Fumarate Drug Combination; Budesonide; Formoterol Fumarate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Carbon; Elements; Inorganic Chemicals; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

Limitations and Caveats not specified

Results Point of Contact

• Title: Isabella Salerio, PhD
• Organization: Zambon SpA

clinicaltrials@zambongroup.com

+39 02665241

Study Officials

• Phil Evans, MBChB

  Quotient Clinical Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 11, 2014
• Study Start: September 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 23, 2022
• Results First Posted: January 26, 2022

Record last verified: 2022-02

Locations

GB (1)