A Study of LY2599506 (Oral Agent Medication: Glucokinase Activator 1) in Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2599506 Given as Monotherapy or in Combination With Metformin in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01029795
• Other study ID #: 13272
• Secondary ID: I2Q-MC-GMAJ
• Status: Terminated
• Phase: Phase 2
• First received: December 9, 2009
• Last updated: November 29, 2011
• Start date: February 2010
• Est. completion date: June 2010

Study information

• Verified date: November 2011
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Comité Ético de Investigación ClínicaSpain: Spanish Agency of MedicinesRussia: Ethics CommitteeRussia: FSI Scientific Center of Expertise of Medical ApplicationRussia: Ministry of Health of the Russian FederationGermany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustralia: National Health and Medical Research CouncilAustria: Agency for Health and Food SafetyHungary: Institutional Ethics CommitteeHungary: National Institute of PharmacyIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to help answer the following research question(s):

• To test if taking LY2599506 for 12 weeks controls blood sugar better than taking glyburide for 12 weeks.

• To evaluate the safety of LY2599506 in participants with diabetes.

• To determine if LY2599506 has the ability to control blood sugar in participants with diabetes.

• To determine how much LY2599506 should be given to participants.

• To determine if LY2599506 has an effect on a participant's weight.

The study design consists of 4 study periods: a screening period, a 4-week dose adjustment period, an 8-week treatment period, and a 4-week follow up period.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Have type 2 diabetes mellitus prior to entering the trial

• Are currently being treated with diet and exercise therapy consistent with the local standards of medical care

• Treated with: Diet and exercise alone; or Diet and exercise in combination with a stable dose of metformin for at least 3 months prior to entering the trial; or Diet and exercise in combination with a stable dose of sulfonylurea for at least 3 months prior to entering the trial; or Diet and exercise in combination with stable doses of metformin and sulfonylurea for at least 3 months prior to entering the trial and have had diabetes for at least 6 years.

• Have an HbA1c value between 7% and 10%

• Are women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Male patients will be advised to use a reliable method of birth control during the study and until 3 months after the last dose of study medication if their partner is of child-bearing potential.

Exclusion Criteria:

• Use of insulin or any antidiabetic agent other than metformin or sulfonylurea during the 3 months prior to entering the trial.

• Have a gastrointestinal disease that significantly impacts gastric emptying or motility (for example, severe gastroparesis or pyloric stenosis), in the opinion of the Investigator, or have undergone gastric bypass or gastric banding surgery.

• Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness

• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.

• Have cardiac autonomic neuropathy (for example, resting tachycardia or orthostatic hypotension), based on clinical signs, symptoms, or appropriate diagnostic testing.

• Have cardiac disease with functional status that is New York Heart Association Class II, III, or IV or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure in the past 6 months.

• Have poorly controlled hypertension (that is, mean systolic blood pressure >160 mm Hg or mean diastolic blood pressure >100 mm Hg) history of malignant hypertension, evidence of renal artery stenosis, and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days before randomization.

• Have fed or fasting state hypertriglyceridemia (defined as >6.8 millimoles per liter [mmol/L], 600 milligrams per deciliter [mg/dL]) at screening. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization.

• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or repeated alanine transaminase (ALT) levels >2.5 times the upper limit of the reference range at screening.

• Have evidence of a significant active, uncontrolled endocrine or autoimmune abnormality, as judged by the Investigator at screening.

• Have an active or untreated malignancy or have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.

• Have a history of seizure disorder.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• LY2599506
Administered orally (po), twice daily (BID) prior to morning and evening meals for 12 weeks
• Glyburide
Administered po, BID daily prior to morning and evening meals for 12 weeks
• Placebo
Matching placebo capsules administered po, BID prior to morning and evening meals for 12 weeks

Locations

Country	Name	City	State
Australia	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.	East Ringwood	Victoria
Australia	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	South Australia
Australia	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.	Heidelberg	Victoria
Austria	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
Czech Republic	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.	Holesov
Czech Republic	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.	Prague
Germany	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	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.	Neuss
Israel	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.	Jerusalem
Israel	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.	Nahariya
Russian Federation	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.	Rostov-On-Don
Russian Federation	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 Petersburg
Spain	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.	Barcelona
Spain	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.	Cordoba
Spain	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.	Dos Hermanas
Spain	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.	Teruel

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Australia,  Austria,  Czech Republic,  Germany,  Israel,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 12 Weeks	Change in HbA1c from baseline following 12 weeks of therapy (HbA1c at week 12 minus HbA1c at baseline). Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 12 weeks	No
Secondary	Change From Baseline in the QT Interval in Electrocardiogram (ECG) at 12 Weeks and 16 Weeks	Measures the QT interval in the ECG. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.	Baseline, 12 weeks, 16 weeks	Yes
Secondary	Change From Baseline in the Homeostasis Model Assessment (HOMA2) Pancreatic Beta Cell Function (%B) at 12 Weeks and 16 Weeks	HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not calculated or analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in the Homeostasis Model Assessment (HOMA2) of Insulin Sensitivity (%S) at 12 Weeks and 16 Weeks	HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population was set at 100%. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not calculated or analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in Triglycerides, Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, Total Cholesterol, and Free Fatty Acids at 12 Weeks and 16 Weeks	Fasting lipids were measured after an overnight fast. Lipids measured included triglycerides, HDL-C, LDL-C, non-HDL-C, total cholesterol, and free fatty acids. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 12 weeks, 16 weeks	Yes
Secondary	Change From Baseline in the European Quality of Life -5 Dimension (EQ-5D) at 12 Weeks and 16 Weeks	Assesses 5 health domains: mobility, self-care, usual activity, pain, and anxiety/depression with 3 options each. Total scores range from 5 (no problem) to 15 (more severe or frequent problems). An algorithm maps the 5 domain outcomes to a single index (0-1). A higher score indicates better perceived health state. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at 12 Weeks and 16 Weeks	DTSQ, an 8-item questionnaire, measures satisfaction with treatment, perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in the Adult Low Blood Sugar Survey (LBSS-33 Item Scale) at 12 Weeks and 16 Weeks	Assesses 2 hypoglycemia domains, with each item score from 0 (never engages in behavior) to 4 (always engages in behavior): Behavioral (15 items; range 0-60) and Worry about hypoglycemia (18 items; range 0-72). Total score is the sum of both domains (range 0-132). Higher scores indicate greater negative impact. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall, and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading. As a result, this outcome measure was not analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Changes From Baseline in the Diabetes Symptoms Checklist-Revised (DSC-R) at 12 Weeks and 16 Weeks	Comprise 6 subscales (34 items). Each item score: 1 (not troublesome) to 5 (extremely troublesome) and transformed to 0-4 scale. Subscale score=sum of item scale in each subscale/total number of items. Global score=sum of scores by dimension. All scores standardized (0-100). Higher scores=greater symptom burden. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in the Perceptions About Medications - Diabetes (PAM-D) Questionnaire at 12 Weeks and 16 Weeks	PAM-D assesses participants' perceptions about their diabetes medications during the past month. Responses ranged from "None of the time," to "All of the time." The sum of all items in the scale equals the scale score, which was linearly transformed to a 0 (least favorable state) to 100 (most favorable state). Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 12 Weeks and 16 Weeks	Change in SBP and DBP following 12 weeks of therapy (Week 12 SBP minus SBP at baseline; Week 12 DBP minus DBP at baseline) and 16 weeks of therapy (Week 16 SBP minus SBP at baseline; Week 16 DBP minus DBP at baseline). Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 12 weeks, 16 weeks	Yes
Secondary	Number of Hypoglycemic Episodes During 12-week Treatment Period and 4-week Follow-up Period	Hypoglycemia was defined as any time a participant felt s/he was experiencing a sign or symptom associated with hypoglycemia or had a blood glucose <70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]) even if it was not associated with signs or symptoms of hypoglycemia. Study GMAJ was terminated after enrolling only 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline through 16 weeks	Yes
Secondary	Change From Baseline in Body Weight at 12 Weeks and 16 Weeks	Weight was measured in the fasting state (with the exception of Visit 1) and after emptying the bladder. Participants were instructed to be lightly clothed and without shoes. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 12 weeks, 16 weeks	No
Secondary	Change From Baseline in the Seven-Point Self-Monitored Blood Glucose (7-point SMBG) at 4 Weeks, 12 Weeks, and 16 Weeks	SMBG levels were measured at the following 7 timepoints during the day: fasting prebreakfast, 2 hours post-breakfast, prior to lunch, 2 hours post-lunch, prior to dinner, 2 hours postdinner, and prior to bed. Study GMAJ was terminated after enrolling only 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 4 weeks, 12 weeks, 16 weeks	No
Secondary	Percentage of Participants With Lipase and Amylase Measurements Above 2-fold Upper Limits of Normal (ULN) During the 12-week Treatment Period	Lipase and amylase concentrations were assessed. Amylase normal limits for males and females are 28-100 units per liter (U/L) (18-50 years), 28-120 U/L (50-60 years), and 28-150 U/L (60-70 years). Normal lipase limits for males and females are 0-100 U/L (18-50 years; 50-60 years) and 0-120 U/L (60-70 years). Study GMAJ was terminated after enrolling only 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline through 12 weeks	Yes
Secondary	Percentage of Participants With Clinically-Significant Elevations of Alanine Aminotransferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT) During the 12-week Treatment Period	Clinically significant elevations of ALT/SGPT were considered =3 times the upper limit of normal (ULN). The percentage of participants above 2- and 5-fold ULN was not analyzed due to the early termination of the trial. The percentage of participants with ALT 3-fold ULN or higher is presented.	Baseline through 12 weeks	Yes
Secondary	Maximum Plasma Concentration (Cmax) at the Steady State for LY2599506	The Cmax value measures the maximum plasma concentration at steady state following administration of doses of LY2599506. Due to the nature of the sparse sampling approach, Cmax was estimated using the posthoc pharmacokinetic (PK) parameters obtained from Population PK (PopPK) modeling. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12	No
Secondary	Area Under the Concentration-Time Curve (AUC) at a Dosing Interval (AUCtau) at the Steady State for LY2599506	The AUCtau values measure the area under the plasma concentration time curve at a dosing interval at steady state for LY2599506. Due to the nature of sparse sampling approach taken for the study AUC tau was estimated using the posthoc pharmacokinetic (PK) parameters obtained from Population PK (Pop PK) modeling. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.	Predose and 2 hours after dosing or predose and 4-12 hours after dosing in weeks 1, 2, 3, and 12	No
Secondary	30-day Adjusted Rates of Self-reported Hypoglycemic Episodes Overall	Hypoglycemia: any time a participant experienced a sign/symptom associated with hypoglycemia or had blood glucose <70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]). The 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days. Study GMAJ was terminated after enrolling 38 participants. Given small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline through 16 weeks	Yes
Secondary	Change From Baseline in Heart Rate at 12 Weeks and 16 Weeks	Heart rate was measured in heartbeats per minute. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 12 weeks, 16 weeks	Yes
Secondary	Mean Morning Dose of LY2599506 During the 12-week Treatment Period	Assigned morning dose, in milligrams (mg), for each participant at each visit. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks.	No
Secondary	Mean Afternoon Dose of LY2599506 During the 12-week Treatment Period	Assigned afternoon dose, in milligrams (mg), for each participant at each visit. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline, 1, 2, 3, 4, 6, 8, 10, 12 weeks.	No
Secondary	Percentage of Participants Requiring Dose Adjustments During the 12-week Treatment Period	Percentage of participants who required dose adjustments at the discretion of the investigator for participants with persistent blood glucose<70 milligrams per deciliter (mg/dL). Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline through 12 weeks	No
Secondary	Mean Total Daily Dose of LY2599506 During the 12-week Treatment Period	The average total daily dose (sum of assigned morning and afternoon doses), in milligrams (mg), at each visit. Study GMAJ was terminated after enrolling 38 participants. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure is not presented.	Baseline through 12 weeks.	No