Trial Outcomes & Findings for Clinical Study to Evaluate Z7200 Pharmacokinetics Profile (NCT NCT02631941)

NCT ID: NCT02631941

Last Updated: 2022-02-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

91 participants

Primary outcome timeframe

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

Results posted on

2022-02-23

Participant Flow

Subjects were screened for eligibility -28 to -2 days prior to the first treatment period. On Day -1 of the first treatment period, i.d. before randomization, subjects were trained on both the RS01 and Symbicort Turbohaler devices.

Subjects had to have an adequate inspiratory flow rate and be able to use both inhalers. Subjects who continued to meet all entry criteria on Day -1 of treatment Period 1 and with an inspiratory flow rate of ≥60 L/min and proper device use entered the treatment phase.

Participant milestones

Participant milestones
Measure	A-B1-B2-C-D 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-C-A-D-B2 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-D-B1-B2-A 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-B2-C-A-B1 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-A-D-B1-C 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-C-B2-B1-A 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-D-A-C-B1 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	A-B2-B1-D-C 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-A-C-B2-D 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-B1-D-A-B2 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).
Overall Study STARTED	9	10	9	9	9	8	9	9	10	9
Overall Study A	9	8	9	9	9	8	9	9	9	9
Overall Study B1	9	10	9	9	8	8	9	9	10	9
Overall Study B2	9	8	9	9	9	8	9	9	9	9
Overall Study C	9	8	9	9	8	8	9	8	9	9
Overall Study D	9	8	9	9	8	8	9	9	9	9
Overall Study COMPLETED	9	8	9	9	8	8	9	8	9	9
Overall Study NOT COMPLETED	0	2	0	0	1	0	0	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	B1-C-A-D-B2 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-A-D-B1-C 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	A-B2-B1-D-C 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-A-C-B2-D 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).
Overall Study Physician Decision	1	0	0	0
Overall Study Adverse Event	1	0	0	0
Overall Study Withdrawal by Subject	0	1	1	0
Overall Study Lost to Follow-up	0	0	0	1

Baseline Characteristics

Clinical Study to Evaluate Z7200 Pharmacokinetics Profile

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A-B1-B2-C-D n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-C-A-D-B2 n=10 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-D-B1-B2-A n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-B2-C-A-B1 n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-A-D-B1-C n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-C-B2-B1-A n=8 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-D-A-C-B1 n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	A-B2-B1-D-C n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-A-C-B2-D n=10 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-B1-D-A-B2 n=9 Participants 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 B1: 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 ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, 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). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	Total n=91 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	9 Participants n=21 Participants	8 Participants n=10 Participants	9 Participants n=115 Participants	9 Participants n=24 Participants	10 Participants n=42 Participants	9 Participants n=42 Participants	91 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Continuous	28.7 years STANDARD_DEVIATION 8.1 • n=5 Participants	29.9 years STANDARD_DEVIATION 9.0 • n=7 Participants	32.9 years STANDARD_DEVIATION 9.4 • n=5 Participants	30.8 years STANDARD_DEVIATION 8.3 • n=4 Participants	23.8 years STANDARD_DEVIATION 3.8 • n=21 Participants	26.1 years STANDARD_DEVIATION 8.5 • n=10 Participants	25.8 years STANDARD_DEVIATION 6.9 • n=115 Participants	31.7 years STANDARD_DEVIATION 7.7 • n=24 Participants	30.7 years STANDARD_DEVIATION 9.7 • n=42 Participants	26.2 years STANDARD_DEVIATION 7.2 • n=42 Participants	28.7 years STANDARD_DEVIATION 8.2 • n=42 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	1 Participants n=42 Participants	29 Participants n=42 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	5 Participants n=21 Participants	6 Participants n=10 Participants	8 Participants n=115 Participants	6 Participants n=24 Participants	7 Participants n=42 Participants	8 Participants n=42 Participants	62 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=24 Participants	2 Participants n=42 Participants	0 Participants n=42 Participants	5 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	6 Participants n=21 Participants	7 Participants n=10 Participants	8 Participants n=115 Participants	8 Participants n=24 Participants	7 Participants n=42 Participants	9 Participants n=42 Participants	77 Participants n=42 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	5 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Region of Enrollment United Kingdom	9 participants n=5 Participants	10 participants n=7 Participants	9 participants n=5 Participants	9 participants n=4 Participants	9 participants n=21 Participants	8 participants n=10 Participants	9 participants n=115 Participants	9 participants n=24 Participants	10 participants n=42 Participants	9 participants n=42 Participants	91 participants n=42 Participants

PRIMARY outcome

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

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal. Treatment B "Number of Participants" counted for both Symbicort 1 and Symbicort 2 treatment group.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-last of Budesonide With and Without Charcoal Blockade	1710 pg*h/mL Geometric Coefficient of Variation 17.9	1710 pg*h/mL Geometric Coefficient of Variation 33.1	1570 pg*h/mL Geometric Coefficient of Variation 20.2	1530 pg*h/mL Geometric Coefficient of Variation 39.7

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-last of Formoterol With and Without Charcoal Blockade	46.1 pg*h/mL Geometric Coefficient of Variation 22.7	52.6 pg*h/mL Geometric Coefficient of Variation 37.3	39.0 pg*h/mL Geometric Coefficient of Variation 25.4	42.8 pg*h/mL Geometric Coefficient of Variation 50.8

PRIMARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Cmax of Budesonide With and Without Charcoal Blockade	1080 pg/mL Geometric Coefficient of Variation 69.8	686 pg/mL Geometric Coefficient of Variation 53.2	1110 pg/mL Geometric Coefficient of Variation 72.8	663 pg/mL Geometric Coefficient of Variation 50.6

PRIMARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Cmax of Formoterol With and Without Charcoal Blockade	10.1 pg/mL Geometric Coefficient of Variation 37.1	11.9 pg/mL Geometric Coefficient of Variation 46.1	10.3 pg/mL Geometric Coefficient of Variation 35.7	11.7 pg/mL Geometric Coefficient of Variation 50.4

SECONDARY outcome

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

Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-30 of Budesonide With and Without Charcoal Blockade.	313 pg*h/mL Geometric Coefficient of Variation 30.5	238 pg*h/mL Geometric Coefficient of Variation 48.9	315 pg*h/mL Geometric Coefficient of Variation 32.5	237 pg*h/mL Geometric Coefficient of Variation 47.5

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-30 of Formoterol With and Without Charcoal Blockade.	3.37 pg*h/mL Geometric Coefficient of Variation 30.1	3.88 pg*h/mL Geometric Coefficient of Variation 42.1	3.36 pg*h/mL Geometric Coefficient of Variation 29.7	3.76 pg*h/mL Geometric Coefficient of Variation 47.9

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=171 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=85 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=85 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-∞ of Budesonide With and Without Charcoal Blockade	1820 pg*h/mL Geometric Coefficient of Variation 18.2	1830 pg*h/mL Geometric Coefficient of Variation 33.0	1670 pg*h/mL Geometric Coefficient of Variation 20.3	1640 pg*h/mL Geometric Coefficient of Variation 38.5

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=163 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=79 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-∞ of Formoterol With and Without Charcoal Blockade	55.4 pg*h/mL Geometric Coefficient of Variation 23.4	63.0 pg*h/mL Geometric Coefficient of Variation 36.0	46.8 pg*h/mL Geometric Coefficient of Variation 26.1	53.7 pg*h/mL Geometric Coefficient of Variation 37.6

SECONDARY outcome

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

Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Tmax for Budesonide With and Without Charcoal Blockade	0.080 hours Interval 0.03 to 0.51	0.250 hours Interval 0.03 to 1.0	0.040 hours Interval 0.03 to 0.75	0.250 hours Interval 0.03 to 1.0

SECONDARY outcome

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

Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=172 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Tmax for Formoterol With and Without Charcoal Blockade	0.080 hours Interval 0.04 to 0.25	0.080 hours Interval 0.03 to 0.33	0.080 hours Interval 0.08 to 0.25	0.080 hours Interval 0.08 to 0.51

SECONDARY outcome

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

Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=87 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=171 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=85 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=85 Participants Symbicort with charcoal (320 ug budesonide)
t1/2 for Budesonide With and Without Charcoal Blockade	3.21 hours Geometric Coefficient of Variation 22.2	3.14 hours Geometric Coefficient of Variation 23.2	3.23 hours Geometric Coefficient of Variation 23.6	3.01 hours Geometric Coefficient of Variation 23.4

SECONDARY outcome

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

Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=163 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=79 Participants Symbicort with charcoal (320 ug budesonide)
t1/2 for Formoterol With and Without Charcoal Blockade	9.35 hours Geometric Coefficient of Variation 25.4	9.28 hours Geometric Coefficient of Variation 26.6	9.45 hours Geometric Coefficient of Variation 27.6	9.08 hours Geometric Coefficient of Variation 26.8

SECONDARY outcome

Timeframe: At 75 min (1.25 hours) post-dose

Population: Safety population: all subjects who received at least one dose (2 inhalations) of investigational medicinal product Treatment B "Number of Participants" counted for both Symbicort 1 and Symbicort 2 treatment groups.

FEV1 refers to the volume of air that an individual can exhale during a forced breath in 1 second. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=88 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=91 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=87 Participants Symbicort with charcoal (320 ug budesonide)
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	0.188 liters Standard Deviation 0.167	0.170 liters Standard Deviation 0.161	0.173 liters Standard Deviation 0.143	0.153 liters Standard Deviation 0.131

SECONDARY outcome

Timeframe: At 75 min (1.25 hours) post-dose

FVC = Forced vital capacity. It is the full amount of air that can be exhaled with effort in a complete breath. FEV1/FVC = Tiffenau-Pinelli Index. This parameter represents the measurement of the amount of air an individual can forcefully exhale from his/her lungs. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=88 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=91 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=87 Participants Symbicort with charcoal (320 ug budesonide)
Change From Baseline in the Ratio of Forced Expiratory Volume in 1 Second to Forced Vital Capacity (FEV1/FVC)	3.94 Ratio Standard Deviation 3.72	3.78 Ratio Standard Deviation 2.90	3.75 Ratio Standard Deviation 2.73	3.83 Ratio Standard Deviation 2.84

SECONDARY outcome

Timeframe: At 75 min (1.25 hours) post-dose

Population: Safety population: all subjects who received at least one dose (2 inhalations) of investigational medicinal product. Treatment B "Number of Participants" counted for both Symbicort 1 and Symbicort 2 treatment groups.

PEFR is the highest rate at which gases can be expelled from the lungs via an open mouth. Its measurement is a simple procedure in which an individual takes a full inspiration and blows out as forcibly as possible into an instrument called a peak flow meter, which measures the maximal gas flow in an exhalation in liters per minute. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Outcome measures
Measure	Treatment A n=88 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=91 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=87 Participants Symbicort with charcoal (320 ug budesonide)
Change From Baseline in Peak Expiratory Flow Rate (PEFR)	32.3 L/min Standard Deviation 42.0	22.4 L/min Standard Deviation 38.7	30.3 L/min Standard Deviation 34.3	19.3 L/min Standard Deviation 39.1

Adverse Events

Treatment A

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Treatment B

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Treatment C

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Treatment D

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Isabella Salerio, PhD

Zambon S.p.A.

Phone: +3902665241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Treatment A n=88 participants at risk Z7200 without charcoal (160 ug budesonide)	Treatment B n=91 participants at risk Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=86 participants at risk Z7200 with charcoal (160 ug budesonide)	Treatment D n=87 participants at risk Symbicort with charcoal (320 ug budesonide)
Nervous system disorders Headache	5.7% 5/88 • Number of events 6 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	6.6% 6/91 • Number of events 7 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	7.0% 6/86 • Number of events 6 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.3% 2/87 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Nervous system disorders Dizziness	2.3% 2/88 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	3.3% 3/91 • Number of events 4 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.3% 2/86 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Nervous system disorders Hypoaesthesia	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	3.3% 3/91 • Number of events 3 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Nervous system disorders Dysgeusia	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Nervous system disorders Presyncope	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Nervous system disorders Somnolence	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Nervous system disorders Tremor	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.2% 2/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.3% 2/88 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.3% 2/86 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Dry Throat	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Nasal Dryness	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
General disorders Vessel puncture site bruise	2.3% 2/88 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.2% 2/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
General disorders Catheter site pain	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
General disorders Vessel puncture site pain	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
General disorders Vessel puncture site rash	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Injury, poisoning and procedural complications Contusion	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Injury, poisoning and procedural complications Skin Abrasion	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.3% 2/87 • Number of events 3 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Injury, poisoning and procedural complications muscle strain	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Injury, poisoning and procedural complications soft tissue injury	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Injury, poisoning and procedural complications Splinter	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Nausea	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.2% 2/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Dyspepsia	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Abdominal discomfort	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Abdominal distension	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Abdominal pain upper	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Gingival Pain	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Gastrointestinal disorders Hypoasthesia oral	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Skin and subcutaneous tissue disorders Blister	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Skin and subcutaneous tissue disorders dermatitis contact	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Skin and subcutaneous tissue disorders Rash	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/87 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Investigations Blood creatine phosphokinase increased	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	2.2% 2/91 • Number of events 2 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Infections and infestations Nasopharyngitis	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/91 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.
Psychiatric disorders Depression	0.00% 0/88 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	1.1% 1/91 • Number of events 1 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/86 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.	0.00% 0/87 • Throughout the study till the end of trial assessment, that is from the first day of screening up to 6 weeks.