IMPERIUM: A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM)
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT02072096
Collaborator
(none)
192
34
2
19.9
5.6
0.3
Study Details
Study Description
Brief Summary
The main purpose of this study is to compare the benefits and risks associated with the use of 2 treatment strategies to lower blood sugar in participants aged 65 and older with T2DM. One strategy is based on the use of oral and injectable medications that only reduce blood sugar (glucose) when it is high. The other strategy is based on non-glucose dependent agents. The trial will last up to 72 weeks for each participant.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
192 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Individualized treatMent aPproach for oldER patIents: A Randomized, Controlled stUdy in Type 2 Diabetes Mellitus (IMPERIUM)
Study Start Date
:
Feb 1, 2014
Actual Primary Completion Date
:
Oct 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Strategy A (Glucose-Dependent) Participants may receive oral and injectable (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) therapies that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. |
Drug: Metformin
Administered orally
Drug: Pioglitazone
Administered orally
Drug: Acarbose
Administered orally
Drug: Linagliptin
Administered orally
Drug: Sitagliptin
Administered orally
Drug: Liraglutide
Administered subcutaneously (SC)
Drug: Exenatide once weekly (QW)
Administered SC
Drug: Exenatide twice daily (BID)
Administered SC
|
| Active Comparator: Strategy B (Reference) Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine is titrated according treatment algorithm. Treatment may last up to 72 weeks. |
Drug: Glimepiride
Administered orally
Drug: Metformin
Administered orally
Drug: Pioglitazone
Administered orally
Drug: Acarbose
Administered orally
Drug: Linagliptin
Administered orally
Drug: Sitagliptin
Administered orally
Drug: Insulin Glargine
Administered SC
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia [Baseline to last participant visit (up to 72 weeks)]
Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c > upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c > upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose <3.0 mmol/L. Success is defined as lacking of failure.
Secondary Outcome Measures
- Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy [Baseline to last participant visit (up to 72 weeks)]
- Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia [Baseline to last participant visit (up to 72 weeks)]
- Change From Baseline of Urinary Albumin to Creatinine Ratio [Baseline, Week 72]
The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease.
- Change From Baseline in Body Mass Index (BMI) [Baseline, Week 72]
- Change From Baseline of Estimated Glomerular Filtration Rate (eGFR) [Baseline, Week 72]
The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease.
Other Outcome Measures
- Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score [Baseline, Week 72]
- Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score [Baseline, Week 72]
- Change From Baseline in Mini-mental State Examination (MMSE) Score [Baseline, Week 72]
Eligibility Criteria
Criteria
Ages Eligible for Study:
65 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes
-
Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening
-
Have an A1c >7.3% and <10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening.
-
Have been treated for at least 3 months prior to the study entry with any of the following treatment options:
-
Diet/exercise only (only if they have known contraindications to metformin treatment)
-
Any dose of sulfonylurea
-
Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective:
-
at least 1500 mg of metformin per day
-
At least 30 mg of pioglitazone per day
-
At least 4 mg of rosiglitazone per day
-
At least 75 mg of acarbose per day
-
Any marketed dose of DPP-4 inhibitor
Exclusion Criteria:
-
Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
-
Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
-
Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization
-
At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA
-
Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2
-
Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry
-
In the opinion of investigator should have an individualized A1c target set at 8% or higher
-
Have a body mass index (BMI) greater than 45 kg/m^2
-
Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study
-
Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification
-
Have an estimated glomerular filtration rate (eGFR) <30 milliliter/minute/1.73 m2 (mL/min/1.73 m2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis
-
Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5 times the upper limit of the reference range)
-
Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer
-
Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days
-
Have any other condition that precludes the participant from following and completing the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Suncoast Research Group, LLC | Miami | Florida | United States | 33135 |
| 2 | New Horizon Research Center | Miami | Florida | United States | 33175 |
| 3 | Suncoast Clinical Research | New Port Richey | Florida | United States | 34652 |
| 4 | Florida Hospital | Orlando | Florida | United States | 32804 |
| 5 | Athens Primary Care | Athens | Georgia | United States | 30606 |
| 6 | Herman Clinical Research, LLC | Suwanee | Georgia | United States | 30024 |
| 7 | Rocky Mountain Diabetes and Osteoporosis Center | Idaho Falls | Idaho | United States | 83404 |
| 8 | Iderc, P.L.C. | Des Moines | Iowa | United States | 50314 |
| 9 | Cotton O'Neil Clinic | Topeka | Kansas | United States | 66606 |
| 10 | Mercy Health Research | Saint Louis | Missouri | United States | 63141 |
| 11 | Southern New Hampshire Diabetes and Endocrinology | Nashua | New Hampshire | United States | 03063 |
| 12 | Heritage Valley Medical Group, Inc. | Beaver | Pennsylvania | United States | 15009 |
| 13 | Family Medical Associates | Levittown | Pennsylvania | United States | 19056 |
| 14 | Carolina Health Specialists | Myrtle Beach | South Carolina | United States | 29572 |
| 15 | Dallas Diabetes Endocrine Center | Dallas | Texas | United States | 75230 |
| 16 | Rockwood Clinic Research Center | Spokane | Washington | United States | 99202 |
| 17 | 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. | Saint Stefan Ob Stainz | Austria | A-8511 | |
| 18 | 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. | Salzburg | Austria | 5026 | |
| 19 | 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. | Vienna | Austria | A-1060 | |
| 20 | 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. | Wien | Austria | A 1210 | |
| 21 | 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. | Berlin | Germany | 10409 | |
| 22 | 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. | Dortmund | Germany | 44137 | |
| 23 | 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. | Hamburg | Germany | 22607 | |
| 24 | 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. | Mainz | Germany | 55116 | |
| 25 | 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. | Münster | Germany | 48145 | |
| 26 | 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. | Neuwied | Germany | 56564 | |
| 27 | 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. | Stuttgart | Germany | 70378 | |
| 28 | Manati Medical Center | Manati | Puerto Rico | 00674 | |
| 29 | American Telemedicine Center | San Juan | Puerto Rico | 00917-3104 | |
| 30 | 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. | Salford | Manchester | United Kingdom | M6 8HD |
| 31 | 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. | Dundee | Scotland | United Kingdom | DD1 9SY |
| 32 | 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. | Sheffield | South Yorkshire | United Kingdom | S5 7AU |
| 33 | 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. | Ipswich | Suffolk | United Kingdom | IP4 5PD |
| 34 | 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. | Manchester | United Kingdom | M41 5SL |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: 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), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02072096
Other Study ID Numbers:
- 14842
- F3Z-MC-IOQL
- 2013-001473-24
First Posted:
Feb 26, 2014
Last Update Posted:
Oct 9, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants completed the first 24 weeks of the study at which time the study was stopped and interim analysis was triggered to assess feasibility. Treatment continued per protocol until study termination and participants discontinued at the next office study visit. Data was assessed from Baseline to last participant visit, up to 72 weeks. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine is titrated according to treatment algorithm. Treatment may last up to 72 weeks. |
| Period Title: Overall Study | ||
| STARTED | 99 | 93 |
| Received at Least One Dose of Study Drug | 98 | 93 |
| COMPLETED | 14 | 15 |
| NOT COMPLETED | 85 | 78 |
Baseline Characteristics
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) | Total |
|---|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine dose is titrated according to treatment algorithm. Treatment may last up to 72 weeks. | Total of all reporting groups |
| Overall Participants | 99 | 93 | 192 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
70.7
(5.3)
|
70.7
(4.4)
|
70.7
(4.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
43
43.4%
|
34
36.6%
|
77
40.1%
|
| Male |
56
56.6%
|
59
63.4%
|
115
59.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
35
35.4%
|
32
34.4%
|
67
34.9%
|
| Not Hispanic or Latino |
63
63.6%
|
59
63.4%
|
122
63.5%
|
| Unknown or Not Reported |
1
1%
|
2
2.2%
|
3
1.6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
1.1%
|
1
0.5%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
6
6.1%
|
10
10.8%
|
16
8.3%
|
| White |
93
93.9%
|
81
87.1%
|
174
90.6%
|
| More than one race |
0
0%
|
1
1.1%
|
1
0.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| Austria |
18
18.2%
|
14
15.1%
|
32
16.7%
|
| Puerto Rico |
23
23.2%
|
16
17.2%
|
39
20.3%
|
| United States |
29
29.3%
|
35
37.6%
|
64
33.3%
|
| United Kingdom |
10
10.1%
|
11
11.8%
|
21
10.9%
|
| Germany |
19
19.2%
|
17
18.3%
|
36
18.8%
|
Outcome Measures
| Title | Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia |
|---|---|
| Description | Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c > upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c > upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose <3.0 mmol/L. Success is defined as lacking of failure. |
| Time Frame | Baseline to last participant visit (up to 72 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 98 | 93 |
| Number (95% Confidence Interval) [percentage of participants] |
64.5
65.2%
|
54.9
59%
|
| Title | Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy |
|---|---|
| Description | |
| Time Frame | Baseline to last participant visit (up to 72 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 98 | 93 |
| Number [percentage of participants] |
21
21.2%
|
13
14%
|
| Title | Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia |
|---|---|
| Description | |
| Time Frame | Baseline to last participant visit (up to 72 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 98 | 93 |
| Total Hypoglycemia |
10
10.1%
|
50
53.8%
|
| Severe Hypoglycemia |
0
0%
|
0
0%
|
| Clinically Significant Hypoglycemia |
0
0%
|
1
1.1%
|
| Symptomatic Hypoglycemia |
5
5.1%
|
34
36.6%
|
| Asymptomatic Hypoglycemia |
8
8.1%
|
30
32.3%
|
| Probable Symptomatic Hypoglycemia |
0
0%
|
7
7.5%
|
| Unspecified Hypoglycemia |
2
2%
|
7
7.5%
|
| Relative Hypoglycemia |
1
1%
|
6
6.5%
|
| Nocturnal Hypoglycemia |
4
4%
|
10
10.8%
|
| Title | Change From Baseline of Urinary Albumin to Creatinine Ratio |
|---|---|
| Description | The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease. |
| Time Frame | Baseline, Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable baseline and post-baseline urinary albumin to creatinine ratio. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 80 | 83 |
| Mean (Standard Deviation) [milligram per millimole (mg/mmol)] |
1.85
(22.99)
|
1.85
(16.46)
|
| Title | Change From Baseline in Body Mass Index (BMI) |
|---|---|
| Description | |
| Time Frame | Baseline, Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable baseline and post-baseline BMI data. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label.Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 96 | 93 |
| Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
-0.47
(1.56)
|
0.20
(2.91)
|
| Title | Change From Baseline of Estimated Glomerular Filtration Rate (eGFR) |
|---|---|
| Description | The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease. |
| Time Frame | Baseline, Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had evaluable baseline and post-baseline eGFR data. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label.Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 85 | 85 |
| Mean (Standard Deviation) [milliliter per minute/1.73 square meter] |
-5.00
(13.64)
|
-5.88
(10.95)
|
| Title | Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score |
|---|---|
| Description | |
| Time Frame | Baseline, Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Unable to conduct change from baseline analysis due to study closure and lack of endpoint data. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score |
|---|---|
| Description | |
| Time Frame | Baseline, Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Unable to conduct change from baseline analysis due to study closure and lack of endpoint data. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label.Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in Mini-mental State Examination (MMSE) Score |
|---|---|
| Description | |
| Time Frame | Baseline, Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Unable to conduct change from baseline analysis due to study closure and lack of endpoint data. |
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) |
|---|---|---|
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. | |||
| Arm/Group Title | Strategy A (Glucose-Dependent) | Strategy B (Reference) | ||
| Arm/Group Description | Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks. | Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks. | ||
All Cause Mortality |
||||
| Strategy A (Glucose-Dependent) | Strategy B (Reference) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Strategy A (Glucose-Dependent) | Strategy B (Reference) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/98 (15.3%) | 14/93 (15.1%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Atrial fibrillation | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Cardiac failure congestive | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Microvascular coronary artery disease | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Myocardial infarction | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Ear and labyrinth disorders | ||||
| Vertigo | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Eye disorders | ||||
| Retinal vascular thrombosis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Gastritis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| General disorders | ||||
| Chest pain | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholecystitis chronic | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Infections and infestations | ||||
| Appendicitis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Cellulitis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Pneumonia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Respiratory tract infection | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Muscle rupture | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Rib fracture | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Road traffic accident | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Investigations | ||||
| Hepatic enzyme increased | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Intervertebral disc protrusion | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Osteoarthritis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Benign neoplasm of spinal cord | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Benign ovarian tumour | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Prostatic adenoma | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Squamous cell carcinoma of lung | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Nervous system disorders | ||||
| Carotid artery stenosis | 1/98 (1%) | 2 | 0/93 (0%) | 0 |
| Cerebrovascular accident | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Syncope | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Transient ischaemic attack | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Pneumonitis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Respiratory failure | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Strategy A (Glucose-Dependent) | Strategy B (Reference) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 82/98 (83.7%) | 74/93 (79.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/98 (1%) | 1 | 2/93 (2.2%) | 2 |
| Iron deficiency anaemia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Lymphadenopathy | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Nephrogenic anaemia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Cardiac disorders | ||||
| Aortic valve stenosis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Atrial fibrillation | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Cardiac failure | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Left ventricular hypertrophy | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Mitral valve incompetence | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Palpitations | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Tachycardia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Type v hyperlipidaemia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Cerumen impaction | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Sudden hearing loss | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Endocrine disorders | ||||
| Goitre | 2/98 (2%) | 2 | 3/93 (3.2%) | 3 |
| Hyperparathyroidism secondary | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Hyperthyroidism | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Hypothyroidism | 1/98 (1%) | 1 | 2/93 (2.2%) | 2 |
| Primary hypothyroidism | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Eye disorders | ||||
| Diplopia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Lacrimation increased | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Vision blurred | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Abdominal distension | 4/98 (4.1%) | 4 | 0/93 (0%) | 0 |
| Abdominal pain | 2/98 (2%) | 2 | 2/93 (2.2%) | 2 |
| Abdominal pain lower | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Abdominal pain upper | 3/98 (3.1%) | 3 | 2/93 (2.2%) | 2 |
| Anal pruritus | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Barrett's oesophagus | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Constipation | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Dental caries | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Diarrhoea | 12/98 (12.2%) | 18 | 6/93 (6.5%) | 6 |
| Dyspepsia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Flatulence | 3/98 (3.1%) | 4 | 1/93 (1.1%) | 1 |
| Food poisoning | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Gastritis | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Gastrointestinal disorder | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Gastrooesophageal reflux disease | 2/98 (2%) | 2 | 2/93 (2.2%) | 2 |
| Haemorrhoids | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Hiatus hernia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Impaired gastric emptying | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Large intestine polyp | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Loose tooth | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Nausea | 7/98 (7.1%) | 8 | 3/93 (3.2%) | 3 |
| Toothache | 3/98 (3.1%) | 3 | 1/93 (1.1%) | 2 |
| Vomiting | 3/98 (3.1%) | 5 | 0/93 (0%) | 0 |
| General disorders | ||||
| Asthenia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Chest pain | 3/98 (3.1%) | 3 | 1/93 (1.1%) | 1 |
| Fatigue | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Influenza like illness | 2/98 (2%) | 3 | 2/93 (2.2%) | 2 |
| Injection site nodule | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Malaise | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Oedema | 6/98 (6.1%) | 7 | 0/93 (0%) | 0 |
| Oedema peripheral | 1/98 (1%) | 1 | 6/93 (6.5%) | 6 |
| Peripheral swelling | 1/98 (1%) | 1 | 2/93 (2.2%) | 2 |
| Pyrexia | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Seasonal allergy | 1/98 (1%) | 1 | 1/93 (1.1%) | 2 |
| Infections and infestations | ||||
| Abscess | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Acarodermatitis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Bronchitis | 4/98 (4.1%) | 6 | 2/93 (2.2%) | 2 |
| Cellulitis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Chikungunya virus infection | 4/98 (4.1%) | 4 | 5/93 (5.4%) | 5 |
| Colon gangrene | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Conjunctivitis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Cystitis | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Dermatitis infected | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Ear infection | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Erysipelas | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Fungal infection | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Fungal skin infection | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Gastroenteritis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Gastroenteritis viral | 1/98 (1%) | 1 | 2/93 (2.2%) | 2 |
| Gastrointestinal infection | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Gingivitis | 2/98 (2%) | 3 | 0/93 (0%) | 0 |
| Helicobacter infection | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Herpes zoster | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Influenza | 4/98 (4.1%) | 4 | 3/93 (3.2%) | 3 |
| Laryngitis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Lower respiratory tract infection | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Lung infection | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Nasopharyngitis | 10/98 (10.2%) | 17 | 16/93 (17.2%) | 18 |
| Onychomycosis | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Rhinitis | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Sinusitis | 3/98 (3.1%) | 3 | 2/93 (2.2%) | 2 |
| Staphylococcal abscess | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Tonsillitis | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Tooth infection | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Upper respiratory tract infection | 3/98 (3.1%) | 3 | 7/93 (7.5%) | 7 |
| Urinary tract infection | 3/98 (3.1%) | 3 | 8/93 (8.6%) | 9 |
| Viral infection | 2/98 (2%) | 2 | 2/93 (2.2%) | 2 |
| Vulvitis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Arthropod bite | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Arthropod sting | 1/98 (1%) | 2 | 0/93 (0%) | 0 |
| Contusion | 3/98 (3.1%) | 3 | 4/93 (4.3%) | 5 |
| Eye contusion | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Fall | 3/98 (3.1%) | 3 | 2/93 (2.2%) | 2 |
| Foot fracture | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Joint dislocation | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Laceration | 1/98 (1%) | 2 | 4/93 (4.3%) | 5 |
| Ligament sprain | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Limb injury | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Meniscus injury | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Post procedural haematoma | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Radius fracture | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Scratch | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Skin abrasion | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Spinal compression fracture | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Investigations | ||||
| Arteriogram coronary | 0/98 (0%) | 0 | 1/93 (1.1%) | 2 |
| Arthroscopy | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Aspiration pleural cavity | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Blood creatinine increased | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Blood glucose abnormal | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Blood glucose increased | 2/98 (2%) | 2 | 1/93 (1.1%) | 1 |
| Blood pressure diastolic decreased | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Blood pressure diastolic increased | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Blood pressure systolic decreased | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Blood pressure systolic increased | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Blood urea increased | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Blood uric acid | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Cardiac imaging procedure | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Catheterisation cardiac | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Gamma-glutamyltransferase increased | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Glomerular filtration rate decreased | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Heart rate increased | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Prostatic specific antigen increased | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Urine analysis abnormal | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Weight decreased | 5/98 (5.1%) | 5 | 0/93 (0%) | 0 |
| Weight increased | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 2/98 (2%) | 3 | 0/93 (0%) | 0 |
| Dehydration | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Fructose intolerance | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Gout | 0/98 (0%) | 0 | 3/93 (3.2%) | 3 |
| Hypercholesterolaemia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Hyperglycaemia | 4/98 (4.1%) | 4 | 0/93 (0%) | 0 |
| Hyperlipidaemia | 3/98 (3.1%) | 3 | 1/93 (1.1%) | 1 |
| Hyperuricaemia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Hypoglycaemia | 0/98 (0%) | 0 | 1/93 (1.1%) | 8 |
| Hyponatraemia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Obesity | 1/98 (1%) | 2 | 0/93 (0%) | 0 |
| Vitamin d deficiency | 9/98 (9.2%) | 9 | 3/93 (3.2%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 4/98 (4.1%) | 4 | 4/93 (4.3%) | 4 |
| Back pain | 9/98 (9.2%) | 9 | 11/93 (11.8%) | 11 |
| Bursitis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Fibromyalgia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Muscle spasms | 2/98 (2%) | 3 | 0/93 (0%) | 0 |
| Muscular weakness | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Musculoskeletal chest pain | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Musculoskeletal pain | 2/98 (2%) | 2 | 1/93 (1.1%) | 1 |
| Myalgia | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Neck pain | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Osteoarthritis | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Osteopenia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Pain in extremity | 2/98 (2%) | 2 | 1/93 (1.1%) | 1 |
| Sjogren's syndrome | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Spinal osteoarthritis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Torticollis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acrochordon | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Basal cell carcinoma | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Benign neoplasm of adrenal gland | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Colon adenoma | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Seborrhoeic keratosis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Squamous cell carcinoma | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Thyroid neoplasm | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Nervous system disorders | ||||
| Amnesia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Autonomic neuropathy | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Carotid artery stenosis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Cerebral haemorrhage | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Dizziness | 4/98 (4.1%) | 4 | 1/93 (1.1%) | 1 |
| Headache | 7/98 (7.1%) | 14 | 1/93 (1.1%) | 1 |
| Paraesthesia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Parkinson's disease | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Polyneuropathy | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Restless legs syndrome | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Sciatica | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Transient ischaemic attack | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Tremor | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Vascular encephalopathy | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Psychiatric disorders | ||||
| Anxiety | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Confusional state | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Depression | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Food aversion | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Insomnia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Sleep disorder | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Renal and urinary disorders | ||||
| Chronic kidney disease | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Hydronephrosis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Hypertonic bladder | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Microalbuminuria | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Nephrolithiasis | 1/98 (1%) | 2 | 0/93 (0%) | 0 |
| Nocturia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Urinary incontinence | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/98 (1%) | 1 | 3/93 (3.2%) | 3 |
| Breast mass | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Prostatitis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Prostatomegaly | 2/98 (2%) | 2 | 0/93 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Chronic obstructive pulmonary disease | 1/98 (1%) | 1 | 1/93 (1.1%) | 2 |
| Cough | 4/98 (4.1%) | 4 | 3/93 (3.2%) | 5 |
| Dry throat | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Dysphonia | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Dyspnoea | 3/98 (3.1%) | 3 | 0/93 (0%) | 0 |
| Dyspnoea exertional | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Emphysema | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Epistaxis | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Nasal congestion | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Oropharyngeal pain | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Respiratory tract congestion | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Rhinitis allergic | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Sleep apnoea syndrome | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis contact | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Eczema | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Nail bed inflammation | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Pruritus generalised | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Urticaria contact | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Surgical and medical procedures | ||||
| Cataract operation | 3/98 (3.1%) | 3 | 2/93 (2.2%) | 4 |
| Coronary angioplasty | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Inguinal hernia repair | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Large intestinal polypectomy | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Lens extraction | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Ptosis repair | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Tendon sheath lesion excision | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Tooth extraction | 0/98 (0%) | 0 | 1/93 (1.1%) | 1 |
| Vascular disorders | ||||
| Arteriosclerosis | 1/98 (1%) | 1 | 1/93 (1.1%) | 1 |
| Essential hypertension | 1/98 (1%) | 1 | 1/93 (1.1%) | 3 |
| Hypertension | 5/98 (5.1%) | 5 | 4/93 (4.3%) | 5 |
| Hypotension | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Peripheral vascular disorder | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
| Peripheral venous disease | 0/98 (0%) | 0 | 2/93 (2.2%) | 2 |
| Subclavian artery stenosis | 1/98 (1%) | 1 | 0/93 (0%) | 0 |
Limitations/Caveats
The trial was terminated per protocol due to lack of feasibility. All participants completed the first 24 weeks of the study. Some participants continued into the Core study. Data was assessed from Baseline to last participant visit, up to 72 weeks.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02072096
Other Study ID Numbers:
- 14842
- F3Z-MC-IOQL
- 2013-001473-24
First Posted:
Feb 26, 2014
Last Update Posted:
Oct 9, 2019
Last Verified:
Sep 1, 2019