Clinical Trials Register

Summary
EudraCT Number:	2010-021516-42
Sponsor's Protocol Code Number:	F3Z-MC-IOQC
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-10-26
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Lithuania - SMCA

A.2

EudraCT number

2010-021516-42

A.3

Full title of the trial

Two Approaches to Escalate Lispro Therapy in Patients with Type 2 Diabetes Mellitus Not Achieving Adequate Glycemic Control on Basal Insulin Therapy and Oral Agents Alone

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Not Applicable

A.3.2

Name or abbreviated title of the trial where available

AUTONOMY

A.4.1

Sponsor's protocol code number

F3Z-MC-IOQC

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Eli Lilly and Company
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Eli Lilly and Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eli Lilly and Company
B.5.2	Functional name of contact point	Carsten Rehn
B.5.3	Address:
B.5.3.1	Street Address	Lilly Corporate Center
B.5.3.2	Town/ city	Indianapolis
B.5.3.3	Post code	IN46285
B.5.3.4	Country	United States
B.5.4	Telephone number	+496172273 2432
B.5.5	Fax number	+496172273 2740
B.5.6	E-mail	rehn_carsten@lilly.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Humalog
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Humalog
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULIN LISPRO
D.3.9.1	CAS number	133107-64-9
D.3.9.2	Current sponsor code	LY275585
D.3.9.3	Other descriptive name	NA
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Lantus
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lantus
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULIN GLARGINE
D.3.9.1	CAS number	160337951
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

type 2 diabetes

Not Applicable

E.1.1.1

Medical condition in easily understood language

type 2 diabetes

Not Applicable

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to compare the change in HbA1c from baseline
(randomization) after 24 weeks of treatment with one of two basal bolus titration algorithms, in adult patients with type 2 diabetes mellitus who have not achieved adequate glycemic control on basal insulin (glargine, NPH, or detemir) with oral antihyperglycemic medications.

E.2.2

Secondary objectives of the trial

Frequency and rate of self-reported hypoglycemic episodes per 30 days and per year
(total, nocturnal, and severe) (overall and in subjects ≥65 years of age)
 change in body weight
 proportions of subjects achieving HbA1c target values (HbA1c ≤7.0% and ≤6.5%) at end of study (overall and in subjects ≥65 years of age)
 time to reach HbA1c target values (HbA1c ≤7.0% and ≤6.5%)
 HbA1c change from baseline (randomization) within each treatment algorithm
 change in fasting glucose (overall and in subjects ≥65 years of age)
 change in 1,5-AG
 7-point SMBG profile data including average blood glucose values for each timepoint measurement
 insulin dose: total, basal (glargine), and prandial (lispro) (24-hour total measured in U/d and U/kg) at end of study.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

[1] Have type 2 diabetes (per World Health Organization [WHO] Classification
of Diabetes).
[2] Are ≥18 and ≤85 years of age at the time of Visit 1.
[3] Have been treated for at least 90 days with insulin (glargine, NPH, NPL, or
detemir) in combination with oral antihyperglycemic agents as monotherapy,
dual, or triple therapy (sulfonylurea, meglitinide, metformin, pioglitazone, or
dipeptidyl peptidase-4 [DPP-4] inhibitor [sitagliptin only]) and, in the opinion of the
investigator, requires further intensification of therapy.
[4] Are treated with insulin (glargine, NPH, NPL or detemir) at least 20 U/day at
study entry.
[5] Have an HbA1c value >7.0% and ≤12.0% according to the central laboratory
at Visit 1 or Visit 6.
Note: for patients who enter the study on NPH, NPL or detemir, BID glargine; or on QD glargine with HbA1c >7.0% and fasting blood glucose >120 mg/dL, a 6-week
lead-in period will be required for glargine optimization. For a patient on QD
glargine with HbA1c >7.0% and fasting blood glucose ≤120 mg/dL, no leadin
period is required and he or she may be randomized at Visit 2.(The FBG measurements are based upon the 3 morning BG measurements from the 7-point SMBG profiles collected on 3 days prior to Visit 2.)
[6] Capable of, and willing, to do the following: inject insulin with a prefilled
pen and perform self blood glucose monitoring and record keeping as required
by this protocol, as determined by the investigator.
[7] Have given written informed consent to participate in this study in accordance
with local regulations.

E.4

Principal exclusion criteria

[8] Prior rapid- or short-acting insulin therapy: patients receiving scheduled
long-term short-acting or rapid-acting or premixed insulin therapy within the
past 6 months will not be eligible to participate in the study. Patients who have previously received short- or rapid-acting insulin as part of short-term
insulin therapy (during gestational diabetes, or during an acute hospitalization
or illness) or occasional use will be allowed to participate in this study.
Occasional use (e.g., used to treat acute hyperglycemia) shall be defined as
less than daily administration of not more than 1 dose per day of short- or
rapid-acting insulin.
[9] Concomitant medications: glucagon-like peptide-1 (GLP-1) receptor
agonist (e.g., exenatide or liraglutide), alpha-glucosidase inhibitor (e.g.,
acarbose, miglitol, or voglibose), DPP-4 inhibitors other than sitagliptin or rosiglitazone use concurrently or within 3 months prior to entry into study.
[10] Severe hypoglycemia: have had more than one episode of severe
hypoglycemia (defined as requiring assistance of a third party due to disabling
hypoglycemia) within 6 months prior to entry into the study.
[11] Excessive insulin resistance: received a total daily dose of insulin >2.0 U/kg
at the time of randomization.
[12] Morbid obesity: defined as a body mass index ≥45 kg/m2.
[13] Malignancy: have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years
[14] Cardiovascular: have cardiac disease with functional status that is New
York Heart Association Class III or IV (per New York Heart Association
[NYHA] Cardiac Disease Classification) or have congestive
heart failure (CHF) requiring pharmacologic treatment or, in the investigator’s
opinion, have severe dependent edema (i.e., edema of the feet or ankles) or
have any condition associated with hypoperfusion, hypoxemia, dehydration,
or sepsis.
[15] Renal: have a history of renal transplantation or are currently receiving renal
dialysis or have serum creatinine ≥2 mg/dL if not on metformin.
[16] Hepatic: have obvious clinical signs or symptoms of liver disease, acute or
chronic hepatitis, or alanine aminotransferase (ALT)/serum glutamic pyruvic
transaminase (SGPT) >3x the upper limit of the reference range as defined by
the central laboratory.
[17] Hematologic: have known hemoglobinopathy or chronic anemia or other
known blood disorder.
[18] Reproductive: (for women) are pregnant or intend to become pregnant
during the course of the study; are sexually active women of childbearing
potential not actively practicing birth control by a method determined by the
investigator to be medically acceptable; or are breastfeeding.
[19] Allergy: have known allergy to insulin lispro, insulin glargine, or excipients
contained in these products.
[20] Glucocorticoid therapy: receiving chronic (lasting longer than 2 weeks)
systemic glucocorticoid therapy (excluding topical and inhaled preparations)
or have received such therapy within 2 weeks immediately before Visit 1.
[21] Adherence to protocol: have any other condition (including known drug or
alcohol abuse or psychiatric disorder) that precludes the patient from
following and completing the protocol.
[22] Prior participation: are currently enrolled in, or have participated in, an
interventional medical, surgical, or pharmaceutical drug or device or off-label
use study (an investigational study in which a medical or surgical treatment
was given) within 30 days prior to entry into the study, or persons who have
previously completed or withdrawn from this study (after having signed the
informed consent document). Patients may be ineligible if they are
concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study.
[23] Non-approved drug: have been treated with a drug within the last 30 days
that has not received regulatory approval at the time of study entry.
[24] Site personnel: investigators or site personnel directly affiliated with this
study and their immediate families. Immediate family is defined as a spouse,
parent, child, or sibling, whether biological or legally adopted.
[25] are employed by Eli Lilly and Company
[26] Screen failure: have previously been screen-failed from this study for any
reason.

E.5 End points

E.5.1

Primary end point(s)

No primary end points

Not Applicable

E.5.1.1

Timepoint(s) of evaluation of this end point

Not Applicable

E.5.2

Secondary end point(s)

Not Applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not Applicable

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

2 escalation algorhythms are compared

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last patient visit after 24 weeks treatment period if no early termination

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	30
F.4.2	For a multinational trial
F.4.2.1	In the EEA	210
F.4.2.2	In the whole clinical trial	1096

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-02-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-11-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-01-14

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