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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00279201




Registration number
NCT00279201
Ethics application status
Date submitted
15/12/2005
Date registered
19/01/2006
Date last updated
21/02/2011

Titles & IDs
Public title
The DURABLE Trial: Evaluating the Durability of Starter Insulin Regimens in Patients With Type 2 Diabetes (IOOV)
Scientific title
The Durability of Twice-Daily Insulin Lispro Low Mixture Compared to Once-Daily Insulin Glargine When Added to Existing Oral Therapy in Patients With Type 2 Diabetes and Inadequate Glycemic Control
Secondary ID [1] 0 0
F3Z-US-IOOV
Secondary ID [2] 0 0
10455
Universal Trial Number (UTN)
Trial acronym
IOOV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Insulin glargine
Treatment: Drugs - Lispro Low Mix
Treatment: Drugs - Lispro Mid Mix
Treatment: Drugs - Lispro

Active comparator: Insulin glargine - Initiation Phase: Insulin glargine for 24 weeks Maintenance: Up to an additional 2 years of insulin glargine if glycosylated hemoglobin (HbA1c) less than or equal to 7.0 at 24 weeks.

Experimental: Lispro Low Mix - Initiation Phase: Lispro Low Mix (LM) for 24 weeks Maintenance Phase: Up to an additional 2 years of Lispro LM if HbA1c less than or equal to 7.0 at 24 weeks.

Experimental: Lispro Mid Mix prior Lispro Low Mix addendum - Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Lispro Mid Mix for 24 weeks in the Intensification Addendum Phase.

Experimental: Lispro Low Mix prior Glargine addendum - Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Lispro Low Mix for 24 weeks in the Intensification Addendum Phase

Active comparator: Basal bolus prior Lispro Low Mix addendum - Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.

Active comparator: Basal bolus prior Glargine addendum - Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.


Treatment: Drugs: Insulin glargine
Subcutaneous injection daily

Treatment: Drugs: Lispro Low Mix
Subcutaneous injection twice daily.

Treatment: Drugs: Lispro Mid Mix
Lispro Mid Mix subcutaneous injection 3 times daily.

Treatment: Drugs: Lispro
Lispro subcutaneous injection 3 times daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
INITIATION: 24-Week Endpoint Glycosylated Hemoglobin (HbA1c)
Timepoint [1] 0 0
Endpoint (Initiation: Week 24)
Primary outcome [2] 0 0
MAINTENANCE: Duration of Time HbA1c Maintained at Goal by Initiation Regimen (Insulin Glargine or Lispro Low Mix)
Timepoint [2] 0 0
Endpoint (Last Observation Carried Forward [LOCF]) (Maintenance: up to 2.5 years)
Primary outcome [3] 0 0
ADDENDUM: 24-Week Endpoint HbA1c
Timepoint [3] 0 0
Endpoint (Addendum) (24 weeks: Week 48)
Secondary outcome [1] 0 0
INITIATION: Change in HbA1c From Baseline to 24 Weeks
Timepoint [1] 0 0
Baseline (Initiation) to Endpoint (LOCF, Week 24)
Secondary outcome [2] 0 0
INITIATION: Percentage of Participants With HbA1c < or = 7.0%, HbA1c <7.0%, and HbA1c < or = 6.5% at Endpoint
Timepoint [2] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [3] 0 0
INITIATION: HbA1c
Timepoint [3] 0 0
Baseline (Initiation), Week 12, Week 24, Endpoint (LOCF)
Secondary outcome [4] 0 0
INITIATION: 7-point Self-monitored Plasma Glucose (SMPG) Profiles and Postprandial Excursions
Timepoint [4] 0 0
Endpoint (LOCF) (Initiation: Week 24)
Secondary outcome [5] 0 0
INITIATION: Change From Baseline to Endpoint in 1,5 Anhydroglucitol (1,5 AG)
Timepoint [5] 0 0
Baseline (Initiation), Endpoint (Week 24)
Secondary outcome [6] 0 0
INITIATION: Incremental Change From Baseline in Body Weight
Timepoint [6] 0 0
Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)
Secondary outcome [7] 0 0
INITIATION: Body Weight
Timepoint [7] 0 0
Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)
Secondary outcome [8] 0 0
INITIATION: Percentage of Participants With Self-reported Hypoglycemic Episodes
Timepoint [8] 0 0
Baseline (Initiation), Endpoint (Week 24), Overall (sum of frequencies of hypoglycemic episodes after baseline ([Week 0]).
Secondary outcome [9] 0 0
INITIATION: Rate of Self-reported Hypoglycemic Episodes
Timepoint [9] 0 0
Endpoint (Initiation: Week 24), Overall (incidence of hypoglycemic episodes after baseline [Week 0])
Secondary outcome [10] 0 0
INITIATION: Insulin Dose
Timepoint [10] 0 0
Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, Endpoint (LOCF)
Secondary outcome [11] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Age
Timepoint [11] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [12] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Origin
Timepoint [12] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [13] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Timepoint [13] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [14] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - HbA1c
Timepoint [14] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [15] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Baseline HbA1c Percentage Group
Timepoint [15] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [16] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - 1,5 AG
Timepoint [16] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [17] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Pre Meals Blood Glucose, Post Meals Blood Glucose, Average of All Blood Glucose, and Fasting Blood Glucose
Timepoint [17] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [18] 0 0
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal - Oral Diabetes Medication at Baseline
Timepoint [18] 0 0
Endpoint (Initiation: Week 24)
Secondary outcome [19] 0 0
MAINTENANCE: HbA1c at Specified Visits and Endpoint
Timepoint [19] 0 0
Baseline (Week 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (up to 2.5 years)
Secondary outcome [20] 0 0
MAINTENANCE: 7-point SMPG Profiles and Postprandial Excursions
Timepoint [20] 0 0
Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)
Secondary outcome [21] 0 0
MAINTENANCE: Rate of Increase in HbA1c
Timepoint [21] 0 0
Endpoint (LOCF) (Maintenance: up to 2.5 years)
Secondary outcome [22] 0 0
MAINTENANCE: Percentage of Participants With HbA1c < or = 7.0%, HbA1c <7.0, and HbA1c < or = 6.5%
Timepoint [22] 0 0
Endpoint (LOCF) (Maintenance: up to 2.5 years)
Secondary outcome [23] 0 0
MAINTENANCE: Incremental Change From Baseline in Body Weight
Timepoint [23] 0 0
Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [24] 0 0
MAINTENANCE: Body Weight
Timepoint [24] 0 0
Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [25] 0 0
MAINTENANCE: Insulin Dose
Timepoint [25] 0 0
Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [26] 0 0
MAINTENANCE: Percentage of Participants With Self-reported Hypoglycemic Episodes
Timepoint [26] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline (Week 0)
Secondary outcome [27] 0 0
MAINTENANCE: Rate of Self-reported Hypoglycemic Episodes
Timepoint [27] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline [Week 0])
Secondary outcome [28] 0 0
MAINTENANCE: Change From Baseline in 1,5-Anhydroglucitol
Timepoint [28] 0 0
Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)
Secondary outcome [29] 0 0
MAINTENANCE: Change From Baseline to Endpoint in HbA1c
Timepoint [29] 0 0
Baseline (Week 0), Week 24, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [30] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes
Timepoint [30] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [31] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes
Timepoint [31] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [32] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group
Timepoint [32] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [33] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group
Timepoint [33] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [34] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c
Timepoint [34] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [35] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c
Timepoint [35] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [36] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group
Timepoint [36] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [37] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group
Timepoint [37] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [38] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline
Timepoint [38] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [39] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline
Timepoint [39] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [40] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG
Timepoint [40] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [41] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG
Timepoint [41] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [42] 0 0
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Mean of Post Meals Blood Glucose and Average of All Blood Glucose
Timepoint [42] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [43] 0 0
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Mean of Post Meals Blood Glucose and Average of All Blood Glucose
Timepoint [43] 0 0
Endpoint (LOCF) (Maintenance) (up to 2.5 years)
Secondary outcome [44] 0 0
ADDENDUM: Change in HbA1c From Point of Second Randomization (Addendum Baseline) to Endpoint
Timepoint [44] 0 0
Baseline (Addendum: Week 24), Endpoint (24 weeks [Week 48])
Secondary outcome [45] 0 0
ADDENDUM: Percentage of Participants With HbA1c < or = 7.0%, HbA1c < 7.0%, and < or = 6.5%
Timepoint [45] 0 0
Endpoint (Addendum: 24 weeks [Week 48])
Secondary outcome [46] 0 0
ADDENDUM: 7-point SMPG Profiles
Timepoint [46] 0 0
Endpoint (Addendum: 24 weeks [Week 48])
Secondary outcome [47] 0 0
ADDENDUM: Incremental Change From Baseline in Body Weight
Timepoint [47] 0 0
Baseline (Addendum: Week 24), Weeks 6 (30 Weeks), 12 (36 Weeks), 24 (48 Weeks), Endpoint (LOCF)
Secondary outcome [48] 0 0
ADDENDUM: Body Weight
Timepoint [48] 0 0
Baseline (Addendum Week 24), Weeks 6 (30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
Secondary outcome [49] 0 0
ADDENDUM: Insulin Dose
Timepoint [49] 0 0
Baseline (Addendum: Week 24), Weeks 1 (25 weeks), 2 (26 weeks), 3 (27 weeks), 4 (28 weeks), 5 (25 weeks), 6 (26 weeks), 8 (32 weeks), 10 (34 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
Secondary outcome [50] 0 0
ADDENDUM: Percentage of Participants With Self-reported Hypoglycemic Episodes
Timepoint [50] 0 0
Weeks 6 (Addendum: 30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
Secondary outcome [51] 0 0
ADDENDUM: Rate of Self-reported Hypoglycemic Episodes
Timepoint [51] 0 0
Endpoint (Addendum 24 weeks), Overall (mean yearly rate of hypoglycemia during addendum phase
Secondary outcome [52] 0 0
ADDENDUM: Change From Baseline in 1,5-Anhydroglucitol to Week 24
Timepoint [52] 0 0
Baseline (addendum: 24 weeks), Endpoint (24 weeks: Week 48)
Secondary outcome [53] 0 0
ADDENDUM: HbA1c at Specified Visits and Endpoint
Timepoint [53] 0 0
Baseline (Addendum: 24 weeks), Weeks 12, 24, Endpoint (24 weeks: Week 48)

Eligibility
Key inclusion criteria
* Must have type 2 diabetes.
* Must be at least 30 and less than 80 years of age at the time of Visit 1.
* Must be on at least two oral antidiabetes medications for at least 90 days.
* Must have an HbA1c 1.2 to 2.0 times the upper limit of normal reference range at the local lab.
Minimum age
30 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Must not have used insulin on a regular basis in the last 12 months.
* Must not have had more than one episode of severe hypoglycemia in the last 24 weeks.
* Must not have a body mass index (BMI) of greater than 45 (morbid obesity).
* Must not have clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease.
* Must not be pregnant or intend to get pregnant during course of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Kingswood Penrith
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Elizabeth Vale
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Keswick
Recruitment hospital [4] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Burnie
Recruitment hospital [5] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Box Hill
Recruitment hospital [6] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Nedlands
Recruitment postcode(s) [1] 0 0
2747 - Kingswood Penrith
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
5035 - Keswick
Recruitment postcode(s) [4] 0 0
7320 - Burnie
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
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Pilar
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Brazil
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Brazil
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Brazil
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São Paulo
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Bangalore
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Coimbatore
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Hyderabaad
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Karnal/Haryana
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India
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Trivandrum
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Netherlands
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Amsterdam
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Brunssum
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Emmen
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Hoogeveen
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Nijmegen
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Venlo
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Carolina
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Ponce
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Romania
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Brasov
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Cluj-Napoca
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Romania
State/province [82] 0 0
Targu-Mures
Country [83] 0 0
Romania
State/province [83] 0 0
Timisoara
Country [84] 0 0
Spain
State/province [84] 0 0
Alcira
Country [85] 0 0
Spain
State/province [85] 0 0
Dos Hermanas
Country [86] 0 0
Spain
State/province [86] 0 0
Madrid
Country [87] 0 0
Spain
State/province [87] 0 0
Malaga
Country [88] 0 0
Spain
State/province [88] 0 0
Mosteles
Country [89] 0 0
Spain
State/province [89] 0 0
Requena
Country [90] 0 0
Spain
State/province [90] 0 0
Santander

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents