ORION: Effects of Cenicriviroc on Insulin Sensitivity in Subjects With Prediabetes or Type 2 Diabetes Mellitus (T2DM) and Suspected NAFLD

Tobira Therapeutics, Inc.45 enrolled

Overview

A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study of cenicriviroc (CVC) to be conducted in approximately 50 adult obese subjects \[body mass index (BMI) ≥ 30 kg/m\^2\] with prediabetes or type 2 diabetes mellitus and suspected NALFD.

Approximately 50 adult obese subjects (BMI ≥ 30 kg/m2) with prediabetes or type 2 diabetes mellitus and suspected NALFD will be randomized into the study. Eligible subjects will receive either CVC (n=25) or matching placebo (n=25), once daily (QD) for 24 weeks, followed by a safety follow-up visit 4 weeks after last intake of study medication.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Prediabetic State Non-alcoholic Fatty Liver Disease Type 2 Diabetes Mellitus

Interventions

Cenicriviroc 150 mgDRUG

Cenicriviroc (CVC) 150 mg, administered orally once daily and taken every morning with food.

PlaceboDRUG

Placebo-matching CVC administered orally once daily and taken every morning with food.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult male and female subjects aged between 18-75 years * Obesity as defined by BMI ≥ 30 kg/m2 * Evidence of prediabetes or type 2 diabetes mellitus based on Screening laboratory values with at least one of the following criteria: * Fasting plasma glucose (FPG) of 100 - 270 mg/dL (5.6 - 15.0 mmol/L) * Hemoglobin A1c (HbA1c) of 5.7 - 10.0% * Participants receiving metformin alone or in combination with a sulfonylurea (glimepiride, glipizide, glyburide, or gliclazide) must be on stable therapy for at least 90 days prior to Screening. * Suspected diagnosis of NAFLD warranting confirmation by liver biopsy * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 upper limit normal (ULN) * Ability to understand and sign a written informed consent form * Females of child-bearing potential and males participating in the study must agree to use at least 2 approved barrier methods of contraception throughout the duration of the study and for 3 months after stopping study drug. Females who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and serum follicle stimulating hormone (FSH) ≥ 30 mU/mL * Participants receiving allowed concomitant medications need to be on stable therapy for 28 days prior to Baseline. Exclusion Criteria: * Use of oral antihyperglycemic agents (OHAs) other than metformin or sulfonylureas, including but not limited to thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, meglitinides, α-glucosidase inhibitors, colesevelam, bromocriptine, pramlintide or basal insulin within 90 days prior to Screening or anticipated use during the trial * Type 1 diabetes * Hepatitis B Surface Antigen (HBsAg) positive * Human Immunodeficiency Virus-1 (HIV-1) or Human Immunodeficiency Virsu-2 (HIV-2) infection * Hepatitis C Virus Antibody (HCVAb) positive * Prior or planned liver transplantation * Other known causes of chronic liver disease, including alcoholic liver disease * History of cirrhosis and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding * Alcohol consumption greater than 14 units/week * Weight reduction through bariatric surgery or planned bariatric surgery during the conduct of the study (including gastric banding) * Any Grade ≥ 3 laboratory abnormality as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Toxicity Grading Scale, except subjects with Grade ≥ 3 dyslipidemia with triglyceride or cholesterol elevations unless clinical assessment foresees an immediate health risk to the subject * Serum albumin \< 3.5 g/dL * Serum creatinine levels ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females if participant is receiving metformin * Estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) equation * Platelet count \< 100,000/mm3 * Hemoglobin \< 12 g/dL for males or \< 11 g/dL for females * Females who are pregnant or breastfeeding * Receiving ongoing therapy with any disallowed medication at Screening * Allergy to the study drug or its components * Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements.

Locations (3)

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Gastroenterology Consultants of San Antonio Digestive Research Center

San Antonio, Texas, United States

Fundacion de Investigacion

San Juan, Puerto Rico

Outcomes

Primary Outcomes

Change From Baseline in Matsuda Index

Change in peripheral insulin sensitivity was measured by the Matsuda Index. Fasting plasma glucose (FPG) and fasting plasma insulin (FPI) concentrations measured during the oral glucose tolerance test (OGTT) were used to calculate the Matsuda Index. Matsuda Index=10,000/square root \[FPG mg/dL x FPI μIU/mL) x (mean glucose mg/dL x mean insulin μIU/mL during OGTT)\]. A Matsuda index of \<2.5 indicates whole body insulin resistance. A lower Matsuda Index indicates the worst disease state. An increase in the Matsuda Index indicates an improvement in insulin sensitivity (best). A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR ) Index

Change in adipose insulin sensitivity was measured by Adipo-IR. Adipo-IR= (Fasting Serum free fatty acid (FFA) mmol/L x FPI μIU/mL). A higher Adipo-IR index indicates the worst disease state. A lower Adipo-IR Index is best. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Secondary Outcomes

Change From Baseline in Macrophage Infiltration in Subcutaneous Adipose Tissue

Macrophage infiltration in adipose tissue was assessed in paraffin-embedded adipose punch biopsies by immunohistochemistry stained for cluster of differentiation 68 (CD68), cluster of differentiation 163 (CD163), C-C chemokine receptor type 2 (CCR2), C-C chemokine receptor type 5 (CCR5) and cluster of differentiation 206 (CD206). A reduction in infiltration indicates less inflammation. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in C-C Chemokine Receptor Type 2 (CCR2) and C-C Chemokine Receptor Type 5 (CCR5) in Subcutaneous Adipose Tissue

Data from ClinicalTrials.gov

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CCR2 and CCR5 corresponding ligands' messenger ribonucleic acid (mRNA) gene expression were assessed in frozen adipose tissue by quantitative polymerase chain reaction (PCR). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Peripheral Monocyte Subsets (CD14/CD16)

Peripheral monocyte subsets (cluster of differentiation 14 (CD14/cluster of differentiation 16 (CD16)\] were measured in fresh peripheral blood mononuclear cells (PBMCs) samples by flow cytometry. Monocyte results are reported for Total, Classical (CD14+CD16-), Intermediate (CD14+CD16+) and Non-classical (CD14lowCD16+). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Fasting Plasma Glucose (FPG)

A fasting blood sample was collected and was sent to a central laboratory for analysis of glucose. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day1) to Weeks 12 and 24

Change From Baseline in Fasting Plasma Insulin (FPI)

A fasting blood sample was collected and was sent to a central laboratory for analysis of insulin. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI)

QUICKI is used to measure insulin sensitivity. QUICKI = 1/(log FPI μIU/mL + log FPG mg/dL). A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline (Day1) to Weeks 12 and 24

Change From Baseline in Homeostasis Model of Insulin Resistance (HOMA-IR)

HOMA-IR = (FPG mg/dL x FPI μIU/mL)/405. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Change From Baseline in Homeostasis Model Assessment of β-cell Function (HOMA-%B)

HOMA-%B= (20 × FPI)/(FPG - 3.5). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Change From Baseline in Fasting Glycosylated Hemoglobin A1c (HbA1c)

Time frame: Baseline (Day 1) to Weeks 12 and 24

Change From Baseline in Plasma Glucagon Concentration

A fasting blood sample was collected and was sent to a central laboratory for analysis of glucagon. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Plasma Glucose at 30, 60, 90 and 120 Minutes Following Glucose Load

Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of glucose.

Time frame: Prior to Glucose Load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Plasma Insulin at 30, 60, 90 and 120 Minutes Following Glucose Load

Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of insulin.

Time frame: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in Area Under the Concentration-time Curve From Time 0 to 120 Minutes [AUC (0-120 Min)] for Serum Glucose

AUC(0-120 min) was derived from the serum glucose values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in Area Under the Concentration-time Curve From Time 30 to 120 Minutes [AUC (30-120 Min)] for Serum Glucose

AUC(30-120 min) was derived from the serum glucose values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in AUC (0-120 Min) for Plasma Insulin

AUC(0-120 min) was derived from the plasma insulin values obtained during the oral glucose tolerance test. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in AUC (30-120 Min) for Plasma Insulin

AUC(30-120 min) was derived from the plasma insulin values obtained during the oral glucose tolerance test. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in Fasting Free Fatty Acids

A fasting blood sample was collected and was sent to a central laboratory for analysis of free fatty acids. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Change From Baseline in Serum Adiponectin Concentration

A fasting blood sample was collected and was sent to a central laboratory for analysis of adiponectin. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline (Day1) to Weeks 12 and 24

Change From Baseline in Serum Resistin Concentration

A fasting blood sample was collected and was sent to a central laboratory for analysis of resistin. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 12 and 24

Serum FFA at 30, 60, 90 and 120 Minutes Following Glucose Load

Blood was collected during the oral glucose tolerance test and was sent to a central laboratory for analysis of FFA.

Time frame: Pre-glucose load, 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in AUC (0-120 Min) for Serum FFA

AUC(0-120 min) was derived from the serum FFA values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in AUC (30-120 Min) for Serum FFA

AUC(30-120 min) was derived from the serum FFA values obtained during the oral glucose tolerance test. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Pre-glucose load) to 30, 60, 90 and 120 minutes after glucose load on Weeks 12 and 24

Change From Baseline in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

Liver biopsy were performed during Screening and at Week 24 only for participants diagnosed with NASH. NAFLD activity score was determined based on 3 components: steatosis (0=\<5% to 3=\>66%), lobular inflammation (0=no foci to 3=\>4 foci/200x) and hepatocellular ballooning (0=none to 2= many cells/prominent ballooning) for a total possible score of 0 to 8. A negative change from Baseline indicates improvement.

Time frame: Baseline (Screening) to Week 24

Number of Participants by NASH Clinical Research Network (CRN) Staging Categories

Liver biopsy were performed during Screening and at Week 24 for participants diagnosed with NASH. The NASH CRN Brunt/Kleiner Fibrosis Staging System Fibrosis Stages are: 0 (None), 1 (Perisinusoidal or periportal), 1A (Mild, zone 3, perisinusoidal), 1B (Moderate, zone 3, perisinusoidal), 1C (Portal/periportal), 2 (Perisinusoidal and portal/periportal), 3 (Bridging fibrosis) and 4 (Cirrhosis).

Time frame: Baseline (Screening) and Week 24

Change From Baseline in Serum C-C Chemokine Receptor Type 2 (CCR2) Ligand: Monocyte Chemotactic Protein 1 (MCP-1)

Blood was collected and was sent to a central laboratory for analysis of MCP-1. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Serum C-C Chemokine Receptor Type 5 (CCR5) Ligand: RANTES

Blood was collected and was sent to a central laboratory for analysis of RANTES (regulated on activation normal T-cell expressed and secreted). A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Alpha (MIP-1α)

Blood was collected and was sent to a central laboratory for analysis of MIP-1α. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Serum CCR5 Ligand: Macrophage Inflammatory Protein 1 Beta (MIP-1β)

Blood was collected and was sent to a central laboratory for analysis of MIP-1β. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Biomarker of Inflammation: Interleukin 1 Beta (IL-1β)

Blood was collected and was sent to a central laboratory for analysis of IL-1β. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Biomarker of Inflammation: Interleukin 6 (IL-6)

Blood was collected and was sent to a central laboratory for analysis of IL-6. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Biomarker of Inflammation: Interleukin 8 (IL-8)

Blood was collected and was sent to a central laboratory for analysis of IL-8. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Biomarker of Inflammation: Interleukin 10 (IL-10)

Blood was collected and was sent to a central laboratory for analysis of IL-1β. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12 and 24

Change From Baseline in Biomarker of Inflammation: High Sensitivity C Reactive Protein (Hs-CRP)

Blood was collected and was sent to a central laboratory for analysis of hs-CRP. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12, 24

Change From Baseline in Biomarker of Inflammation: Tumor Necrosis Factor Alpha (TNF-α)

Blood was collected and was sent to a central laboratory for analysis of TNF-α. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Weeks 2, 12, 24

Change From Baseline in Noninvasive Metabolic Biomarker: Hyaluronic Acid

Blood was collected and was sent to a central laboratory for analysis of Hyaluronic Acid. A positive change from Baseline indicates improvement and a negative change from Baseline indicates improvement.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Noninvasive Metabolic Biomarker: Cytokeratin-18 (CK-18) [M30 and M65]

Blood was collected and was sent to a central laboratory for analysis of CK-18. A positive change from Baseline indicates improvement and a negative change from Baseline indicates improvement.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Noninvasive Metabolic Biomarker: Fibroblast Growth Factor-21 (FGF-21)

Blood was collected and was sent to a central laboratory for analysis of FGF-21. A negative change from Baseline indicates improvement and a positive change from Baseline indicates improvement.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Noninvasive Metabolic Biomarker: Mac-2 Binding Protein (Mac-2BP)

Blood was collected and was sent to a central laboratory for analysis of Mac-2BP. A negative change from Baseline indicates improvement and a positive change from Baseline indicates improvement.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Noninvasive Metabolic Serum Biomarker: Cluster of Differentiation (CD95)

Blood was collected and was sent to a central laboratory for analysis of CD95. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Noninvasive Metabolic Marker: Alpha-fetoprotein (AFP)

Blood was collected and was sent to a central laboratory for analysis of AFP. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline (Day 1) to Week 24

Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Fat Fraction

LiverMultiscan™ tests via MRI were obtained at Baseline and at Weeks 12 and 24. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Corrected T1 (cT1)

LiverMultiscan™ via MRI were obtained at Baseline and at Weeks 12 and 24. The mean of 4 regions of interest as selected by the technician is reported. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: cT1 Mode Values Within the Liver

LiverMultiscan™ via MRI were obtained at Baseline and at Weeks 12 and 24. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Liver Inflammation and Fibrosis (LIF) Score

LiverMultiscan™ tests via MRI were obtained at Baseline and at Weeks 12 and 24. The mean of 4 regions of interest as selected by the technician is reported. The LIF Score ranges from 0=no liver disease to 4=severe liver disease. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Change From Baseline in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) Test: Iron Content

LiverMultiscan™ tests via MRI were obtained at Baseline and at Weeks 12 and 24. A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Change From Baseline in Body Weight

A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

Change From Baseline in Liver Transaminase: Alanine Aminotransferase (ALT)

Blood was collected and was sent to a central laboratory for analysis of ALT. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Change From Baseline in Liver Transaminase: Aspartate Aminotransferase (AST)

Blood was collected and was sent to a central laboratory for analysis of AST. A negative change from Baseline indicates improvement and a positive change from Baseline indicates a worsening.

Time frame: Baseline to Weeks 12 and 24

Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)

An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs or worsens after receiving study drug.

Time frame: 24 weeks

Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs

Vital signs included Systolic Blood Pressure, Diastolic Blood Pressure, Heart Rate, Respiratory Rate and Temperature. The investigator determined if the vital sign measurements were clinically relevant.

Time frame: 24 weeks

Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results

A standard 12 lead ECG was performed. The investigator determined if the abnormal results were clinically significant.

Time frame: Baseline 24 weeks

Plasma Cenicriviroc Concentrations

Time frame: Baseline (Day 1) one sample predose; Weeks 2, 12 and 24 one sample predose and one sample postdose

Number of Participants With Abnormal Physical Examination Findings

Physical examination included assessment of the following body systems: Abdomen, Cardiovascular, Extremities, Head, Eyes, Ears, Nose, Throat, Lungs, Lymph Nodes, Neurological, Skin and Thyroid. The number of participants with any abnormal findings at Baseline and participants with any abnormal findings Post-Baseline are reported.

Time frame: 24 weeks