The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.

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1 The clinical trial infrmatin prvided in this public disclsure synpsis is supplied fr infrmatinal purpses nly. Please nte that the results reprted in any single trial may nt reflect the verall ptential risks r benefits f a prduct which are based n an evaluatin f an entire research prgram. Befre prescribing any Takeda prducts, healthcare prfessinals shuld cnsult prescribing infrmatin fr the prduct apprved in their cuntry.

2 N. 279/NRP-001 Clinical Reprt 2.0 SYNOPSIS STUDY INFORMATION: Name f Spnsr: Takeda Pharmaceutical Cmpany Limited, 1-1, Dshmachi 4-chme, Chu-ku, Osaka , Japan Title f : A t Explre the Effects f Azilsartan Cmpared t Telmisartan n Insulin Resistance f Patients with Essential Hypertensin n Type 2 Diabetes Mellitus by HOMA-R (AT-HOMA) Name f Active Ingredient: Azilsartan Name f Finished Prduct: Azilsartan Investigatrs: Principal investigatrs f 17 study sites enrlled subjects int the study Sites: A ttal 17 study sites in Japan enrlled subjects int the randmized treatment perid Publicatin Based n the (Citatin): Nt applicable Perid: Date First Subject Signed Infrmed Cnsent Frm: 04 June 2014 Date f Last Subject s Last Dse: 25 April 2016 Phase f Develpment: Phase 4 Objectives: T explre the effects f azilsartan 20 mg, cmpared with telmisartan 40 mg, nce daily rally fr 12 weeks, n insulin resistance in subjects with grade I r II essential hypertensin cmplicated by type 2 diabetes mellitus. Methdlgy: This was a multicenter, phase 4, randmized, pen-label, parallel-grup explratry study t explre the effects f azilsartan 20 mg, cmpared with telmisartan 40 mg, n insulin resistance in subjects with grade I r II essential hypertensin cmplicated by type 2 diabetes mellitus. Subjects were randmized in a 1:1 rati t receive either telmisartan 40 mg r azilsartan 20 mg. Randmizatin was stratified by: Hmestasis Mdel Assessment Rati (HOMA-R) at the start f treatment (less than 2.5 vs. 2.5 r higher) Cncurrent use f ral hypglycemic agents (use vs. nn-use f biguanides). Allcated antihypertensives were taken rally, nce daily, befre r after breakfast in the mrning fr 12 weeks. On scheduled visits, subjects were instructed t return t the investigatinal site withut taking the mrning dse f their allcated drug; they then received the dse after cmpleting the specified tests/examinatins. Subjects were screened fr eligibility after they had prvided infrmed cnsent. Any ral antihypertensive medicatins used by subjects at the time f infrmed cnsent had t be discntinued fr at least 2 weeks prir t the start f study treatment. Treatment with ral hypglycemic agents used at the time f infrmed cnsent was cntinued, but the dsage and administratin f such agents culd nt be changed during the study. visits, during which subjects underwent examinatins and assessments as utpatients, tk place every 4 weeks accrding t the study schedule f assessments, with the first (baseline) visit perfrmed befre administratin f the allcated antihypertensive medicatin. An additinal ptinal visit was scheduled n Week 2 if cnsidered necessary fr safety reasns by the principal investigatr r investigatr. Number f Subjects: Planned (as Randmized): 40 subjects Signed Infrmed Cnsent Frm: 78 subjects

3 N. 279/NRP-001 Clinical Reprt Randmized t Treatment: 33 subjects Analyzed: Full Analysis Set (FAS): 33 subjects Safety Analysis Set (SAS): 33 subjects Diagnsis and Main Criteria fr Inclusin: Subjects were utpatients, aged 20 years r lder at the time f cnsent, diagnsed with grade I r II essential hypertensin (sitting systlic bld pressure f 130 mmhg and <180 mmhg, r sitting diastlic bld pressure f 80 mmhg and <110 mmhg at the start f the treatment perid) and type 2 diabetes. All subjects were required t have an HbA1c level (NGSP value) f <8.4% with a 0.3% change in HbA1c (peak minus nadir), and n change in diet/exercise therapy (if applicable), during the 3 mnths befre infrmed cnsent. The main exclusin criteria were: grade II essential hypertensin fr which antihypertensive drug(s) were used; use f ral antihypertensive medicatin within 2 weeks befre the start f the treatment perid; use f renin-angitensin system (RAS) inhibitrs r thiazlidines within 3 mnths befre the start f the treatment perid; type 1 diabetes; fasting bld glucse f <180 mg/dl and HOMA-R f 1.6 at the start f the treatment perid; receiving r requiring treatment with insulin, glucagn-like peptide-1 (GLP-1) receptr agnists r ther parenteral hypglycemic agents, r cmbinatin therapy with 3 r mre ral hypglycemic agents; and a change in antidiabetic medicatin (including dsage change) within 3 mnths befre the start f the treatment perid. Duratin f Treatment: 12 weeks Test Prduct, Dse and Mde f Administratin, and Lt Number: Drugs Prduct Dse Strength and Frm Dsage Azilsartan 20 mg tablet 20 mg nce daily Mde f Administratin Oral Manufacturer Takeda Pharmaceutical Cmpany Limited Reference Therapy, Dse and Mde f Administratin, and Lt Number: Drugs Prduct Dse Strength and Frm Dsage Telmisartan 40 mg tablet 40 mg nce daily Mde f Administratin Oral Manufacturer Nippn Behringer Ingelheim Cmpany Limited Criteria fr Evaluatin: Efficacy: Primary Endpint: Change in insulin resistance index (HOMA-R*) Change frm the start f the treatment perid at the end f the treatment perid *HOMA-R = fasting insulin (µu/ml) fasting glucse (mg/dl) / 405 Secndary Endpints: Change in fasting bld glucse, fasting insulin, HbA1c (NGSP value), HOMA-β*, and 1,5-AG Change frm the start f the treatment perid t the end f the treatment perid *HOMA-β = fasting insulin (μu/ml) 360 / (fasting glucse [mg/dl] 63)

4 N. 279/NRP-001 Clinical Reprt Other Endpints: Change in ffice bld pressure and sitting pulse rate measured during physical examinatin, early mrning and befre-bedtime bld pressure and sitting pulse rate measured using a hme sphygmmanmeter, bld urea nitrgen level (hereinafter, BUN), serum creatinine level, highmlecular-weight adipnectin level, plasma aldsterne level, plasma renin activity, high-sensitive C- reactive prtein level (hereinafter, CRP), urinary albumin/creatinine rati*, urinary Na/creatinine rati**, and estimated glmerular filtratin rate (hereafter, egfr) Change frm the start f the treatment perid t the end f the treatment perid *Urinary albumin/creatinine rati (mg/g Cr) = Urinary albumin (mg) / Urinary creatinine (mg/dl) **Urinary Na/creatinine rati (g/day) = Urinary Na (meq/l) / Urinary creatinine (mg/dl) Percentage change in ttal chlesterl level, HDL level, LDL level, fasting triglyceride level, and nn- HDL chlesterl level Percentage change frm the start f the treatment perid t the end f the treatment perid Subjects with nrmal bld pressure (clinic and hme). Safety: Adverse events (AEs) Statistical Methds: Efficacy: The FAS, defined as all enrlled subjects wh received either the investigatinal prduct r cmparatr at least nce during the study after randmizatin, was used fr all efficacy analyses. Primary Endpint: In the primary analysis, summary statistics fr the primary endpint were calculated fr each treatment grup. A tw-sided 95% cnfidence interval (CI) fr the pint estimate and the difference in mean change in HOMA-R between the tw treatment grups (change in the azilsartan grup minus the change in the telmisartan grup) was als determined. In the secndary analysis, summary statistics fr the primary endpint were calculated fr each treatment grup by setting the baseline HOMA-R values (less than 2.5 r 2.5 r higher) and cncurrent use f biguanides (yes r n) as stratified factrs. Secndary and Other Efficacy Endpints: Summary statistics were calculated fr each treatment grup. In additin, a tw-sided 95% CI fr the pint estimate and the difference in mean change between the tw treatment grups (change in the azilsartan grup minus the change in the telmisartan grup) was determined fr each endpint. Safety: The SAS, defined as all enrlled subjects wh received either the investigatinal prduct r cmparatr at least nce during the study, was used fr all safety analyses. AEs were cded using the Medical Dictinary fr Regulatry Activities/Japanese editin (MedDRA/J) versin An AE was defined as any untward medical ccurrence in a subject receiving a drug; it did nt necessarily have t have a causal relatinship with this treatment. Incidences f AEs were tabulated by System Organ Class (SOC) and Preferred Term (PT) fr each treatment grup as fllws: all AEs, severity f AEs, drug-related AEs, severity f drug-related AEs, AEs leading t discntinuatin f treatment, and serius AEs (SAEs). SUMMARY OF RESULTS: Baseline Demgraphics and Other Relevant Characteristics: Demgraphic and ther baseline characteristics were similar between the tw treatment grups and representative f the ppulatin under study, except fr: HOMA-R, which was higher in the azilsartan 20 mg grup (mean: 4.24 [SD: 1.843]) than in the telmisartan 40 mg grup (mean: 3.31 [SD: 1.366]); and duratin f hypertensin, which was shrter in the azilsartan 20 mg grup (mean: 3.54 years [SD: 4.392]) cmpared with the telmisartan 40 mg grup (mean: 4.71 years [SD: 4.391]).

5 N. 279/NRP-001 Clinical Reprt Subject Dispsitin: A ttal f 78 subjects signed the infrmed cnsent frm. Of these subjects, 33 met the eligibility criteria and were randmized int the run-in phase f the study. Overall, 16 subjects were randmized t receive telmisartan 40 mg and 17 subjects were randmized t receive azilsartan 20 mg. Tw subjects in the azilsartan 20 mg grup did nt cmplete study treatment, as defined in the prtcl: ne due t an AE (mild bld pressure decreased) and ne due t vluntary withdrawal. All subjects in the telmisartan 40 mg grup cmpleted planned study treatment. Efficacy Results: In the primary analysis, the mean (95% CI) changes in HOMA-R frm baseline t the end f treatment were (-0.72, 0.27) in the telmisartan 40 mg grup and 0.22 (-1.09, 1.52) in the azilsartan 20 mg grup Neither change was cnsidered t be clinically relevant The mean (95% CI) difference in the changes frm baseline in HOMA-R between the azilsartan and telmisartan grups was 0.44 (-0.89, 1.78). N clinically significant differences in the change in mean HOMA-R frm baseline t the end f treatment were bserved between the tw treatment grups in subgrups stratified accrding t baseline HOMA-R values (less than 2.5 vs. 2.5 r higher) r cncurrent use f biguanides (yes vs. n). Hwever, verall sample sizes in the subgrups f subjects with baseline HOMA-R values less than 2.5 (7 subjects verall) r cncurrent use f biguanides (7 subjects verall) were t small t allw meaningful treatment cmparisns. Neither telmisartan nr azilsartan had cnsistent r clinically significant effects n the secndary efficacy endpints. Mean (95% CI) changes in secndary efficacy endpints frm the start t the end f the treatment perid in the telmisartan 40 mg grup and azilsartan 20 mg grup were, respectively: Fasting bld glucse: (-9.05, 6.93) and 2.00 (-7.76, 11.76) mg/dl Fasting insulin: (-2.289, 0.654) and (-2.927, 3.877) μu/ml HBA1c (NGSP value): 0.10% (-0.05%, 0.25%) and 0.09% (-0.11%, 0.28%) HOMA-β: -3.88% (-14.62%, 6.86%) and -0.44% (-16.95%, 16.07%) 1,5-AG: 0.24 (-0.90, 1.39) and (-1.96, 0.65) μg/ml. Treatment with either f the tw allcated antihypertensive medicatins resulted in a reductin in mean systlic and diastlic bld pressure (clinic) frm baseline t the end f treatment, with numerically greater reductins bserved in the azilsartan 20 mg grup: Mean (95% CI) changes in systlic bld pressure (clinic) frm the start t the end f the treatment perid were (-16.4, -4.7) mmhg in the telmisartan 40 mg grup and (- 23.6, -6.4) mmhg in the azilsartan 20 mg grup Mean (95% CI) changes in diastlic bld pressure (clinic) frm the start t the end f treatment were -7.2 (-10.2, -4.1) mmhg in the telmisartan 40 mg grup and -9.8 (-14.6, -5.0) mmhg in the azilsartan 20 mg grup. A similar reductin in mean mrning systlic and diastlic bld pressure (hme) frm baseline t the end f treatment was bserved in the tw treatment grups: Mean (95% CI) changes in mrning systlic bld pressure (hme) frm the start t the end f the treatment perid were (-10.23, 1.44) mmhg in the telmisartan 40 mg grup and (-14.74, 2.02) mmhg in the azilsartan 20 mg grup Mean (95% CI) changes in mrning diastlic bld pressure (hme) frm the start t the end f treatment were (-7.60, 0.26) mmhg in the telmisartan 40 mg grup and (-8.66, 0.69) mmhg in the azilsartan 20 mg grup.

6 N. 279/NRP-001 Clinical Reprt A reductin in mean befre-bedtime systlic and diastlic bld pressure (hme) frm baseline t the end f treatment was als seen in bth treatment grups. Mean (95% CI) changes in befre-bedtime systlic bld pressure (hme) frm the start t the end f the treatment perid were (-16.63, -3.16) mmhg in the telmisartan 40 mg grup and (-20.92, -5.48) mmhg in the azilsartan 20 mg grup Mean (95% CI) changes in befre-bedtime diastlic bld pressure (hme) frm the start t the end f treatment were (-9.61, -1.31) mmhg in the telmisartan 40 mg grup and (-12.82, -3.33) mmhg in the azilsartan 20 mg grup. There were n clinically meaningful changes in sitting pulse rate (clinic r hme [mrning and befrebedtime] measurements) in either treatment grup ver the study perid. At the end f the study, 3 f 16 evaluable subjects in the telmisartan 40 mg grup (18.8%) and 5 f 16 subjects in the azilsartan 20 mg grup (31.3%) had nrmal clinic bld pressure values. Fr hmerecrded bld pressure, 2 f 14 evaluable subjects in the telmisartan 40 mg grup (14.3%) and 2 f 15 subjects in the azilsartan 20 mg grup (13.3%) had nrmal values at the end f treatment. Safety Results: Except fr the change frm baseline t end f treatment in mean plasma renin activity, which was higher in the azilsartan 20 mg grup than in the telmisartan 40 mg grup (7.223 [95% CI: 1.367, ] vs [95% CI: , 6.555] ng/ml/hr, respectively), there were n clinically meaningful differences between the tw treatment grups fr all ther clinical labratry parameters specified as ther efficacy endpints (change frm baseline t end f treatment in BUN, serum creatinine, ttal chlesterl, HDL chlesterl, LDL chlesterl, fasting triglycerides, high-mlecular-weight adipnectin, plasma aldsterne, high-sensitive CRP, urinary albumin/creatinine rati, urinary Na/creatinine rati, egfr, and nn-hdl chlesterl). Eight subjects in the telmisartan 40 mg grup (50.0%) and six subjects in the azilsartan 20 mg grup (35.3%) experienced a TEAE. The mst cmmn TEAE by PT was naspharyngitis, which was bserved in 2 subjects in the telmisartan 40 mg grup (12.5%) and 2 subjects in the 20 mg azilsartan grup (11.8%). N ther TEAEs were reprted in mre than 1 subject. All TEAEs were mild r mderate in intensity. One subject in the azilsartan 20 mg grup (5.9%) experienced a TEAE (mild bld pressure decreased) that was cnsidered related t the study drug and which resulted in discntinuatin f treatment. N ther drug-related TEAEs r TEAEs leading t discntinuatin f study treatment were bserved. N deaths r serius TEAEs were reprted in the study. Cnclusins regarding clinical labratry tests and vital signs are presented in the Efficacy Results. CONCLUSIONS: Over the 12-week treatment perid, HOMA-R levels in the azilsartan 20 mg grup were nt reduced, but thse in the telmisartan 40 mg grup were lwered in subjects with grade I r II essential hypertensin cmplicated by type 2 diabetes mellitus. Bth azilsartan 20 mg and telmisartan 40 mg exerted antihypertensive effects, and a number f subjects achieved nrmal bld pressure thrughut the entire treatment perid. Azilsartan 20 mg and telmisartan 40 mg were well tlerated, and n new safety signals were identified. DATE OF REPORT: 26 June 2017