Clinical trial NCT02631941
Conditions: Asthma
Sponsor: Zambon SpA
Start date: 2016-01-01; Completion date: 2016-07-01
Enrollment: 91 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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.

Detailed description:
This was a single center, open label, randomized, five-period crossover, single-dose study in healthy volunteers aged 18 to 45 years. A total of 90 volunteers were planned to be enrolled, with 9 subjects in each of the 10 treatment sequences.

The study consisted of 5 treatment periods, each lasting approximately 48h, separated by a washout period of a minimum of 5 days. RS01 and/or Symbicort Turbohaler device use training was provided on Day -1 and Day 1 of each treatment period. Subjects were screened for eligibility to participate in the study -28 to -2 days prior to the first treatment period, and were randomized to one of 10 treatment sequences containing the following 5 treatment arms on Day 1 of the first treatment period:

Treatment A: Z7200 without oral activated charcoal\* Treatment B1: Symbicort 1 without oral activated charcoal\* Treatment B2: Symbicort 2 without oral activated charcoal\* Treatment C: Z7200 with oral activated charcoal\*\* Treatment D: Symbicort with oral activated charcoal\*\*

Subjects were admitted to the clinical unit at 8.00 on the morning of Day -1, and were dosed on the morning of Day 1 following an overnight fast (minimum of 8h). On Day 2, following collection of the 24-h PK blood sample, subjects were discharged.

\* Subjects who received treatments A, B1 and B2 rinsed their mouth vigorously with 50 mL water for 3 to 5 sec immediately after the second inhalation.

\*\* A charcoal blockade was used to prevent absorption from oropharyngeal and GI tract, in order to assess the pulmonary deposition of budesonide and formoterol, with periods performed without a charcoal blockade allowing the assessment of the total systemic exposure to the drug.

Arms: arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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. arm 5: 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. arm 6: 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. arm 7: 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. arm 8: 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. arm 9: 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. arm 10: 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.
Interventions: intervention 1: Z7200 without oral activated charcoal intervention 2: Symbicort Turbohaler without oral activated charcoal intervention 3: Z7200 with oral activated charcoal intervention 4: Symbicort Turbohaler with oral activated charcoal
Intervention descriptions: intervention 1: 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). intervention 2: 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 denote Symbicort without oral activated charcoal administered in two different periods). intervention 3: 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). intervention 4: 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).

Protocol documents: