Trial Outcomes & Findings for Afrezza Safety and Pharmacokinetics Study in Pediatric Patients (NCT NCT02527265)
NCT ID: NCT02527265
Last Updated: 2021-04-06
Results Overview
Insulin Cmax after a dose of Afrezza
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
250 minutes post-dose
Results posted on
2021-04-06
Participant Flow
A total of 48 subjects were screened for the study, of which 30 subjects were enrolled in the study (15 subjects each in Cohort 1 and Cohort 2)
Participant milestones
| Measure |
Afrezza Cohort 1 (Ages 13-17)
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive daily injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive daily injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
13
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Afrezza Safety and Pharmacokinetics Study in Pediatric Patients
Baseline characteristics by cohort
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive daily injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=15 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive daily injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
15.0 years
STANDARD_DEVIATION 1.73 • n=5 Participants
|
10.4 years
STANDARD_DEVIATION 1.55 • n=7 Participants
|
12.7 years
STANDARD_DEVIATION 2.84 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 250 minutes post-dosePopulation: All subjects without any major deviations related to study drug administration, and for whom any PK parameters are available, will be included in the PK population. Subjects who sneeze or cough right after AFREZZA inhalation for PK profiling will be considered as important deviations related to IMP and will be excluded for PK analysis.
Insulin Cmax after a dose of Afrezza
Outcome measures
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=13 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Insulin Maximum Observed Concentration (Cmax)
4 unit cartridge
|
28.5 μU/mL
Standard Deviation 5.77
|
102 μU/mL
Standard Deviation 31.4
|
|
Insulin Maximum Observed Concentration (Cmax)
8 unit cartridge
|
101 μU/mL
Standard Deviation 42.1
|
133 μU/mL
Standard Deviation 91.0
|
|
Insulin Maximum Observed Concentration (Cmax)
12 unit cartridge
|
201 μU/mL
Standard Deviation 118
|
251 μU/mL
Standard Deviation NA
n=1
|
|
Insulin Maximum Observed Concentration (Cmax)
16 unit cartridge
|
105 μU/mL
Standard Deviation NA
n=1
|
—
|
SECONDARY outcome
Timeframe: 250 minutes post-dosePopulation: All subjects without any major deviations related to study drug administration, and for whom any PK parameters are available, will be included in the PK population. Subjects who sneeze or cough right after AFREZZA inhalation for PK profiling will be considered as important deviations related to IMP and will be excluded for PK analysis.
Insulin Tmax after a dose of Afrezza
Outcome measures
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=13 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Insulin Time to Reach Cmax (Tmax)
12 unit cartridge
|
15.3 minutes
Standard Deviation 3.27
|
10.0 minutes
Standard Deviation NA
n=1
|
|
Insulin Time to Reach Cmax (Tmax)
16 unit cartridge
|
20.0 minutes
Standard Deviation NA
n=1
|
—
|
|
Insulin Time to Reach Cmax (Tmax)
4 unit cartridge
|
12.5 minutes
Standard Deviation 3.54
|
9.5 minutes
Standard Deviation 4.04
|
|
Insulin Time to Reach Cmax (Tmax)
8 unit cartridge
|
13.5 minutes
Standard Deviation 5.47
|
14.1 minutes
Standard Deviation 5.44
|
SECONDARY outcome
Timeframe: 250 minutes post-dosePopulation: All subjects without any major deviations related to study drug administration, and for whom any PK parameters are available, will be included in the PK population. Subjects who sneeze or cough right after AFREZZA inhalation for PK profiling will be considered as important deviations related to IMP and will be excluded for PK analysis.
Insulin AUC after a dose of Afrezza
Outcome measures
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=13 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Insulin Area Under Concentration Time Curve (AUC)
4 unit cartridge
|
1468 min*μU/mL
Standard Deviation 1272
|
2931 min*μU/mL
Standard Deviation 1011
|
|
Insulin Area Under Concentration Time Curve (AUC)
8 unit cartridge
|
4488 min*μU/mL
Standard Deviation 2644
|
4975 min*μU/mL
Standard Deviation 2921
|
|
Insulin Area Under Concentration Time Curve (AUC)
12 unit cartridge
|
6400 min*μU/mL
Standard Deviation 3009
|
5971 min*μU/mL
Standard Deviation NA
n=1
|
|
Insulin Area Under Concentration Time Curve (AUC)
16 unit cartridge
|
5778 min*μU/mL
Standard Deviation NA
n=1
|
—
|
SECONDARY outcome
Timeframe: Using PK data collected over 250 minutes post-dose of AfrezzaPopulation: All subjects without any major deviations related to study drug administration, and for whom any PK parameters are available, will be included in the PK population. Subjects who sneeze or cough right after AFREZZA inhalation for PK profiling will be considered as important deviations related to IMP and will be excluded for PK analysis.
FDKP (inert carrier excipient) calculated half life t1/2
Outcome measures
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=13 Participants
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Assessment of Fumaryl Diketopiperazine (FDKP) Elimination Half-life (t1/2)
4 unit cartridge
|
103 minutes
Standard Deviation 23.0
|
86.8 minutes
Standard Deviation 6.35
|
|
Assessment of Fumaryl Diketopiperazine (FDKP) Elimination Half-life (t1/2)
8 unit cartridge
|
123 minutes
Standard Deviation 31.3
|
86.5 minutes
Standard Deviation 15.8
|
|
Assessment of Fumaryl Diketopiperazine (FDKP) Elimination Half-life (t1/2)
12 unit cartridge
|
109 minutes
Standard Deviation 25.9
|
95.5 minutes
Standard Deviation NA
n=1
|
|
Assessment of Fumaryl Diketopiperazine (FDKP) Elimination Half-life (t1/2)
16 unit cartridge
|
144 minutes
Standard Deviation NA
n=1
|
—
|
Adverse Events
Afrezza Cohort 1 (Ages 13-17)
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Afrezza Cohort 2 (Ages 8-12)
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 participants at risk
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=15 participants at risk
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
Other adverse events
| Measure |
Afrezza Cohort 1 (Ages 13-17)
n=15 participants at risk
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
Afrezza Cohort 2 (Ages 8-12)
n=15 participants at risk
Individualized dose of Afrezza (Technosphere Insulin) for each patient at each meal (breakfast, lunch, and dinner) for 30 days.
During the trial, all patients will receive multiple injections of basal long acting insulin, in general at bedtime every day.
Afrezza: Pharmaceutical form: powder
Route of administration: inhalation
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
46.7%
7/15 • Number of events 7 • 4 weeks
|
33.3%
5/15 • Number of events 5 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
6.7%
1/15 • Number of events 2 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Infections and infestations
Gastroenteritis
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
20.0%
3/15 • Number of events 3 • 4 weeks
|
|
Infections and infestations
Urinary tract infection
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
General disorders
Asthenia
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
General disorders
Tenderness
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Investigations
Blood pressure increased
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Investigations
Urine cotinine test positive
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
13.3%
2/15 • Number of events 2 • 4 weeks
|
0.00%
0/15 • 4 weeks
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/15 • 4 weeks
|
6.7%
1/15 • Number of events 1 • 4 weeks
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
66.7%
10/15 • Number of events 48 • 4 weeks
|
66.7%
10/15 • Number of events 45 • 4 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place