Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

Figures & data

Figure 1. Study design of three pivotal phase three studies (ABS-AS-301, ABS-AS-304 and ABS-AS-307). HFA, hydrofluoroalkane; MDI, metered-dose inhaler; MDPI, multidose dry powder inhaler; PRN, as needed; QID, four times a day. ^aAll patients were provided with an albuterol HFA MDI to use as needed for breakthrough asthma symptoms. ^bFinal follow-up of adverse events was conducted 3 (±1) days after the last treatment visit.

Figure 2. Patient disposition for the integrated safety population. MDPI, multidose dry powder inhaler; QID, four times a day. ^aOne patient in one of the 12-week double-blind studies took both albuterol MDPI and placebo MDPI in error and was therefore included in both treatment groups of the safety population. Thus, 321 patients were treated with albuterol MDPI 180 µg QID and 333 patients were treated with placebo MDPI.

Table 1. Demographic characteristics (12-week integrated safety population).

Characteristic	Albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) (n = 321)	Placebo MDPI (n = 333)	Total (n = 653)^a
Age, years
Mean (SD)	37.5 (16.3)	37.7 (15.8)	37.6 (16.0)
12–17, n (%)	55 (17)	50 (15)	105 (16)
18–64, n (%)	252 (79)	273 (82)	524 (80)
≥65, n (%)	14 (4)	10 (3)	24 (4)
Sex, n (%)
Male	139 (43)	130 (39)	268 (41)
Female	182 (57)	203 (61)	385 (59)
Race, n (%)
White	238 (74)	254 (76)	491 (75)
Black	70 (22)	70 (21)	140 (21)
Other^b	13 (4)	9 (3)	22 (3)
Ethnicity, n (%)
Hispanic or Latino	39 (12)	37 (11)	75 (11)
Not Hispanic or Latino	282 (88)	296 (89)	578 (89)
BMI, mean (SD), kg/m^2	28.4 (7.0)	28.8 (6.8)	28.6 (6.9)

BMI, body mass index; MDPI, multidose dry powder inhaler; SD, standard deviation.

^aOne patient randomized to albuterol MDPI in the 52-week safety study was assigned an incorrect medication kit and was also treated with placebo MDPI. This patient is included in each treatment group but is counted only once for the overall total.

^bOther includes Asian, American Indian, Alaskan Native and Pacific Islander.

Table 2. Adverse events (12-week integrated safety population).

	Number (%) of patients
Event	Albuterol MDPI 180 μg (2 inhalations  × 90 μg/inhalation) (n = 321)	Placebo MDPI (n = 333)
≥1 Adverse event	128 (40)	166 (50)
≥1 Adverse event leading to withdrawal from study	3 (<1)	2 (<1)
≥1 Serious adverse event	2 (<1)	1 (<1)
Adverse events in >2% of patients in either treatment group (preferred term)
Upper respiratory tract infection	31 (10)	38 (11)
Nasopharyngitis	17 (5)	21 (6)
Headache	13 (4)	19 (6)
Oropharyngeal pain	11 (3)	13 (4)
Cough	10 (3)	13 (4)
Sinusitis	8 (2)	14 (4)
Influenza	5 (2)	13 (4)
Bronchitis	3 (<1)	11 (3)

MDPI, multidose dry powder inhaler.

Table 3. Adverse events related to β₂-adrenergic agonists (12-week integrated safety population).

	Number (%) of patients
Preferred term	Albuterol MDPI 180 μg (2 inhalations × 90 μg/ inhalation) (n = 321)	Placebo MDPI (n = 333)
Headache	13 (4)	19 (6)
Sinus headache	4 (1)	3 (<1)
Migraine	2 (<1)	3 (<1)
Anxiety	2 (<1)	0
Feeling jittery	2 (<1)	0
Tremor	2 (<1)	0
Arthralgia	1 (<1)	4 (1)
Myalgia	1 (<1)	3 (<1)
Hypertension	1 (<1)	2 (<1)
Increased blood pressure	1 (<1)	1 (<1)
Muscle spasms	1 (<1)	1 (<1)
Angina pectoris	1 (<1)	0
Hot flush	1 (<1)	0
Hypokalemia	1 (<1)	0
Insomnia	1 (<1)	0
Palpitations	1 (<1)	0
Paresthesia	1 (<1)	0
Peripheral edema	1 (<1)	0
Dizziness	0	2 (<1)
Nerve compression	0	1 (<1)
Orthostatic intolerance	0	1 (<1)
Syncope	0	1 (<1)
Tension headache	0	1 (<1)

MDPI, multidose dry powder inhaler.

Table 4. Adverse events occurring in >2% of patients treated with albuterol MDPI PRN during the open-label phase of the 52-week safety study.

Preferred term	Albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) Open-label phase Weeks 13–52  n = 168^a Number (%) of patients
Nasopharyngitis	20 (12)
Sinusitis	19 (11)
Upper respiratory tract infection	15 (9)
Cough	11 (7)
Oropharyngeal pain	10 (6)
Headache	10 (6)
Pyrexia	7 (4)
Bronchitis	6 (4)
Abdominal pain upper	6 (4)
Arthralgia	5 (3)

MDPI, multidose dry powder inhaler; PRN, as needed; QID, four times daily.

^aPatients enrolled in the albuterol MDPI QID arm during the 12-week double-blind phase (n = 168); 156 of those patients continued in the open-label phase of the study and received albuterol MDPI PRN.