Trial Outcomes & Findings for Efficacy and Safety of Prandial Inhalation of Technosphere/Insulin in Combination With Metformin or Technosphere/Insulin Alone Versus 2 Oral Anti-Diabetic Agents in Subjects With Type 2 Diabetes (NCT NCT00332488)

NCT ID: NCT00332488

Last Updated: 2014-10-16

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

547 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2014-10-16

Participant Flow

31 May 2006 (first subject enrolled) to 03 Mar 2008 (last subject completed. Multi-national trial conducted in Argentina, Brazil, Canada, Chile, Czech Republic, Mexico, Poland, Russian Federation, Spain, Ukraine, and USA.

2 week screening period prior to randomization. 1512 patients screened with 528 patients randomized. 977 patients failed screening criteria, 9 subjects passed screening but were not randomized, 2 subjects failed screening but were randomized.

Participant milestones

Participant milestones
Measure	TI Inhalation Powder Alone Technosphere® Insulin Inhalation Powder administered prior to each meal without any other anti-diabetic treatment; dose individualized for each subject	Metformin & Secretagogues Metformin (\>= 1,000 mg/day or maximum tolerate dose) \& Secretagogue (Sulfonylurea or meglitinide at \>= half maximum manufacturer recommended dose or maximum tolerated dose)	TI Inhalation Powder + Metformin Technosphere® Insulin Inhalation Powder administered prior to each meal (dose individualized for each subject) \& Metformin (\>= 1,000 mg/day or maximum tolerate dose)
Initial Treatment Phase (Weeks 0 - 12) STARTED	183	170	175
Initial Treatment Phase (Weeks 0 - 12) COMPLETED	133	152	119
Initial Treatment Phase (Weeks 0 - 12) NOT COMPLETED	50	18	56
Transfer Treatment Phase (Weeks 12 - 24) STARTED	29	72	254
Transfer Treatment Phase (Weeks 12 - 24) COMPLETED	27	70	233
Transfer Treatment Phase (Weeks 12 - 24) NOT COMPLETED	2	2	21

Reasons for withdrawal

Reasons for withdrawal
Measure	TI Inhalation Powder Alone Technosphere® Insulin Inhalation Powder administered prior to each meal without any other anti-diabetic treatment; dose individualized for each subject	Metformin & Secretagogues Metformin (\>= 1,000 mg/day or maximum tolerate dose) \& Secretagogue (Sulfonylurea or meglitinide at \>= half maximum manufacturer recommended dose or maximum tolerated dose)	TI Inhalation Powder + Metformin Technosphere® Insulin Inhalation Powder administered prior to each meal (dose individualized for each subject) \& Metformin (\>= 1,000 mg/day or maximum tolerate dose)
Initial Treatment Phase (Weeks 0 - 12) Adverse Event	8	2	6
Initial Treatment Phase (Weeks 0 - 12) Physician Decision	13	2	10
Initial Treatment Phase (Weeks 0 - 12) Withdrawal by Subject	21	10	20
Initial Treatment Phase (Weeks 0 - 12) Various	4	0	20
Initial Treatment Phase (Weeks 0 - 12) Lost to Follow-up	1	3	0
Initial Treatment Phase (Weeks 0 - 12) Protocol Violation	3	1	0
Transfer Treatment Phase (Weeks 12 - 24) Adverse Event	0	0	3
Transfer Treatment Phase (Weeks 12 - 24) Lost to Follow-up	0	0	1
Transfer Treatment Phase (Weeks 12 - 24) Physician Decision	0	0	3
Transfer Treatment Phase (Weeks 12 - 24) Protocol Violation	0	0	1
Transfer Treatment Phase (Weeks 12 - 24) Withdrawal by Subject	2	2	8
Transfer Treatment Phase (Weeks 12 - 24) Various	0	0	5

Baseline Characteristics

Efficacy and Safety of Prandial Inhalation of Technosphere/Insulin in Combination With Metformin or Technosphere/Insulin Alone Versus 2 Oral Anti-Diabetic Agents in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TI Inhalation Powder Alone n=177 Participants	Metformin & Secretagogues n=162 Participants	TI Inhalation Powder + Metformin n=169 Participants	Total n=508 Participants Total of all reporting groups
Age, Continuous	57.3 years n=5 Participants	57.6 years n=7 Participants	56.8 years n=5 Participants	57.2 years n=4 Participants
Sex: Female, Male Female	93 Participants n=5 Participants	88 Participants n=7 Participants	101 Participants n=5 Participants	282 Participants n=4 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	74 Participants n=7 Participants	68 Participants n=5 Participants	226 Participants n=4 Participants
Body Weight	86.1 kilograms STANDARD_DEVIATION 15.6 • n=5 Participants	84.2 kilograms STANDARD_DEVIATION 16.2 • n=7 Participants	83.9 kilograms STANDARD_DEVIATION 13.9 • n=5 Participants	84.8 kilograms STANDARD_DEVIATION 15.27 • n=4 Participants
Fasting Plasma Glucose	193.5 milligrams per deciliter STANDARD_DEVIATION 52.4 • n=5 Participants	194.6 milligrams per deciliter STANDARD_DEVIATION 48.5 • n=7 Participants	188.6 milligrams per deciliter STANDARD_DEVIATION 49.7 • n=5 Participants	192.2 milligrams per deciliter STANDARD_DEVIATION 50.23 • n=4 Participants
HbA1c	8.9 percentage STANDARD_DEVIATION 0.95 • n=5 Participants	8.9 percentage STANDARD_DEVIATION 0.94 • n=7 Participants	9.0 percentage STANDARD_DEVIATION 0.97 • n=5 Participants	8.9 percentage STANDARD_DEVIATION 0.95 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: Intention to Treat (ITT) Population with Last Observation Carried Forward

Outcome measures

Outcome measures
Measure	Metformin & Secretagogues n=162 Participants Metformin \& Secretagogues	TI Inhalation Powder + Metformin n=169 Participants Technosphere® Insulin Inhalation Powder \& Metformin	TI Inhalation Powder + Metformin Technosphere® Insulin Inhalation Powder \& Metformin
Difference in Change From Baseline for HbA1c Between TI+ Metformin and Metformin+Secretagogue	-0.78 Percentage of total hemoglobin 95% Confidence Interval -0.78 • Interval -0.92 to -0.64	-0.70 Percentage of total hemoglobin 95% Confidence Interval -0.70 • Interval -0.84 to -0.56	—

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Intention to Treat (ITT) Population for patients with available data

(Change from baseline within TI Alone) minus (change from baseline within metformin + secretagogue)

Outcome measures

Outcome measures
Measure	Metformin & Secretagogues n=133 Participants Metformin \& Secretagogues	TI Inhalation Powder + Metformin n=153 Participants Technosphere® Insulin Inhalation Powder \& Metformin	TI Inhalation Powder + Metformin Technosphere® Insulin Inhalation Powder \& Metformin
Difference in Change From Baseline for HbA1c Between TI Alone and Metformin+Secretagogue	0.12 Percentage of total hemoglobin Standard Deviation 1.3	-0.76 Percentage of total hemoglobin Standard Deviation 0.92	—

SECONDARY outcome

Timeframe: Week 24

Population: Intent to Treat: Subjects who stayed on original treatment

Outcome measures

Outcome measures
Measure	Metformin & Secretagogues n=29 Participants Metformin \& Secretagogues	TI Inhalation Powder + Metformin n=72 Participants Technosphere® Insulin Inhalation Powder \& Metformin	TI Inhalation Powder + Metformin n=77 Participants Technosphere® Insulin Inhalation Powder \& Metformin
Change in HbA1c From Baseline to Week 24 (Subjects Who Stayed on Original Treatment)	-1.82 percentage of total hemoglobin Standard Deviation 1.114	-1.23 percentage of total hemoglobin Standard Deviation 1.080	-1.68 percentage of total hemoglobin Standard Deviation 1.014

Adverse Events

TI Inhalation Powder Alone

Serious events: 5 serious events

Other events: 72 other events

Deaths: 0 deaths

Metformin & Secretagogues

Serious events: 5 serious events

Other events: 42 other events

Deaths: 0 deaths

TI Inhalation Powder + Metformin

Serious events: 11 serious events

Other events: 138 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TI Inhalation Powder Alone n=181 participants at risk Technosphere® Insulin Inhalation Powder	Metformin & Secretagogues n=166 participants at risk Metformin \& Secretagogues	TI Inhalation Powder + Metformin n=351 participants at risk Technosphere® Insulin Inhalation Powder \& Metformin
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	3.9% 7/181 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	7.2% 12/166 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	2.3% 8/351 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.
Infections and infestations NASOPHARYNGITIS	2.2% 4/181 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	7.8% 13/166 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	5.1% 18/351 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.
Metabolism and nutrition disorders HYPOGLYCAEMIA	13.3% 24/181 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	12.7% 21/166 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	23.9% 84/351 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.
Respiratory, thoracic and mediastinal disorders COUGH	27.1% 49/181 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	3.6% 6/166 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.	17.7% 62/351 • From first dose until 30 days after last dose of study medication Subjects in the TI Alone and Metformin + Secretagogue arms may have transferred to the TI + Metformin Arm for study period 2. There are 181, 166 and 351 subjects in the TI Alone, Metformin + Secretagogue and TI + Metformin treatment arms, respectively, across all 24 weeks of the study.

Additional Information

Chief Medical Officer

MannKind Corporation

Phone: 201-983-5000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MannKind has right to 1st joint multicenter publication. After 1st publication PI may publish data only if PI submits proposed publication to MNKD for review 60 days prior to publication date. MNKD may remove any confidential information. If a multicenter publication is not submitted 12 months after conclusion, abandonment, or termination of the Study at all sites, or if MNKD confirms there will be no multicenter Study publication, PI may publish the Study results subject to MNKD rights herein.
Publication restrictions are in place

Restriction type: OTHER