Supplementary Online Content

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1 Supplementary Online Content Block GA, Bushinsky DA, Cunningham J, et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: two randomized clinical trials. JAMA. doi: /jama eappendix. Supplementary Methods etable 1. Number of Randomized Patients by Country etable 2. Summary of Dose Level of Study Medication etable 3. Summary of Dialysate Calcium Concentration etable 4. Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase and Collagen Type I Cross-Linked C-Telopeptide etable 5. Summary of Low Corrected Calcium During the Study etable 6. Treatment Emergent Adverse Events ( 1% in Arm in at Least One Study) in Descending Order of Frequency etable 7. Summary of Corrected QT Interval (Bazett and Fridericia) efigure 1. Time to >30% Reduction From Baseline in PTH (Rolling Average of 3 PTH Values Were Used to Compare With Baseline) efigure 2 A-B. Forest Plot for Difference in Proportion With >30% Decrease From Baseline in PTH Across Patient Subgroups efigure 3 A-B. Use of Calcium Supplement or Calcium Containing Phosphate Binders Over Time efigure 3 C-D. Use of Active Vitamin D Over Time efigure 4. Mean PTH Value (pg/ml) (95% CI) by Study Week This supplementary material has been provided by the authors to give readers additional information about their work.

2 eappendix. Supplementary Methods Inclusion Criteria Patient understands the study procedures and agrees to participate in the study by giving written informed consent. 18 years of age or older. Female patients who are post-menopausal (post-menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, have a medical condition that prevents pregnancy, remain abstinent, or are willing to use highly effective contraception during the study and for 3 months after the last dose. Women of child-bearing potential must have a negative serum pregnancy test within 2 weeks prior to the first dose of investigational product. Patient receiving active vitamin D sterols must have had no more than a maximum dose change of 50% within the 4 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol. Patient receiving phosphate binders must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol. Patient receiving calcium supplements must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments and remain stable through randomization.

3 Patient must be receiving hemodialysis 3 times weekly for at least 3 months and have adequate hemodialysis with a delivered Kt/V 1.2 or urea reduction ratio (URR) 65% within 4 weeks prior to screening laboratory assessments. Dialysis prescription dialysate calcium concentration must be 2.25 meq/l and stable for at least 4 weeks prior to screening laboratory assessments, remain stable through randomization and remain 2.25 meq/l for the duration of the study. Patient must have 2 consecutive screening predialysis serum PTH labs drawn on separate days within 2 weeks prior to randomization and the results of both must be > 400 pg/ml. Enrollment of patients with mean screening ipth > 1000 pg/ml will be limited to approximately 20% of patients. Patient must have 2 consecutive screening predialysis serum albumin-corrected calcium labs drawn on separate days within 2 weeks prior to randomization and the results of both must be 8.3 mg/dl. Patient agrees to not participate in another study of an investigational agent during the study. Patient s legally acceptable representative has provided informed consent when the patient has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the patient to give written informed consent. Exclusion Criteria Currently receiving treatment in another investigational device or drug study, or ended treatment on another investigational device or drug study(s) within 8 weeks prior to screening. Other investigational procedures while participating in this study are excluded. Anticipated or scheduled parathyroidectomy during the study period. Patient has received a parathyroidectomy within 3 months prior to dosing.

4 Anticipated or scheduled kidney transplant during the study period. Patient has known sensitivity to any of the products or components to be administered during dosing. Patient has previously been randomized in this study. Patient has received AMG 416 in a prior clinical trial of AMG 416 (also referred to as KAI- 4169). Patient has received cinacalcet within the 4 weeks prior to screening labs (treatment with cinacalcet is prohibited during the study). Patient has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator. Patient has a history of any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the patient. Patient history of malignancy within the last 5 years (except non-melanoma skin cancers, or cervical carcinoma in situ). Patient has a serious concurrent medical condition (e.g., malignancy) likely to result in death during the next 12 months. Patient is pregnant or nursing. Patient has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes. Patient s screening 12-lead electrocardiogram (ECG) suggests unstable arrhythmia or other cardiac abnormality that could place the patient at increased risk, based upon the Investigator s opinion. Patient has poorly controlled hypertension.

5 Patient has a history within the past 6 months of either angina pectoris with symptoms that occur at rest or minimal activity, or congestive heart failure (New York Heart Association Classification III or IV). Patient has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening. Patient is receiving treatment for a seizure disorder or has a history of a seizure within the last 12 months prior to screening. Patient has had surgery (except minor surgery) within the last 8 weeks prior to screening. Patient has clinically significant abnormalities on prestudy clinical examination or abnormalities on the most recent central laboratory test during the screening period prior to randomization according to the Investigator including but not limited to the following: o Serum albumin 3.0 g/dl o Serum magnesium < 1.5 mg/dl o Serum transaminase (alanine transaminase [ALT] or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic oxaloacetic transaminase [SGOT]) > 2.5 times the upper limit of normal (ULN) at screening Patient likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient and Investigator s knowledge. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion

6 etable 1. Number of Randomized Patients by Country Country (N = 508) (N = 515) Australia 15 (3.0) 17 (3.3) Austria 10 (2.0) 0 (0.0) Belgium 23 (4.5) 20 (3.9) Canada 11 (2.2) 13 (2.5) Czech Republic 18 (3.5) 16 (3.1) France 9 (1.8) 16 (3.1) Germany 15 (3.0) 1 (0.2) Hungary 27 (5.3) 25 (4.9) Israel 6 (1.2) 9 (1.7) Italy 19 (3.7) 9 (1.7) Netherlands 0 (0.0) 12 (2.3) Poland 23 (4.5) 35 (6.8) Russian Federation 38 (7.5) 20 (3.9) Spain 34 (6.7) 34 (6.6) Sweden 0 (0.0) 5 (1.0) United Kingdom 10 (2.0) 0 (0.0) United States 250 (49.2) 283 (55.0)

7 etable 2. Summary of Dose Level of Study Medication Dose (mg) per administration Week 1 (N = 251) (N = 252) n Median (Q1, Q3) 5.0 (5.0, 5.0) 5.0 (5.0, 5.0) Week 5 n Median (Q1, Q3) 7.5 (5.0, 10.0) 7.5 (5.0, 10.0) Week 9 n Median (Q1, Q3) 7.5 (5.0, 10.0) 7.5 (5.0, 10.0) Week 13 n Median (Q1, Q3) 7.5 (5.0, 12.5) 7.5 (2.5, 12.5) Week 17 n Median (Q1, Q3) 7.5 (2.5, 12.5) 7.5 (2.5, 12.5) Week 20 n Median (Q1, Q3) 7.5 (2.5, 12.5) 7.5 (2.5, 10.0) Week 23 n Median (Q1, Q3) 7.5 (2.5, 10.0) 5.0 (2.5, 10.0) Week 26 n Median (Q1, Q3) 7.5 (2.5, 10.0) 5.0 (2.5, 10.0) N: patients who received at least one dose of investigational product

8 etable 3. Summary of Dialysate Calcium Concentration Dialysate Calcium Concentration (N = 251) (N = 254) (N = 252) (N = 259) Baseline (meq/l) < (5.2) 18 (7.1) 24 (9.5) 28 (10.8) (71.3) 180 (70.9) 142 (56.3) 159 (61.4) > (23.5) 56 (22.0) 85 (33.7) 72 (27.8) Missing 0 (0.0) 0 (0.0) 1 (0.4) 0 (0.0) End of Study (meq/l) < (4.0) 19 (7.5) 16 (6.3) 27 (10.4) (59.0) 177 (69.7) 106 (42.1) 157 (60.6) > (37.0) 58 (22.8) 129 (51.2) 75 (29.0) Missing 0 (0.0) 0 (0.0) 1 (0.4) 0 (0.0) N: patients who received at least one dose of investigational product

9 etable 4. Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase and Collagen Type I Cross-Linked C-Telopeptide Bone-Specific Alkaline Phosphatase Change from Baseline to Week 12 (mcg/l) (N = 254) (N = 254) (N = 255) (N = 260) n Median Q1, Q3-2.66, , , , 6.12 Percent Change from Baseline to Week 12 (%) n Median Q1, Q , , , , Change from Baseline to Week 27 (mcg/l) n Median Q1, Q , , , , 9.00 Percent Change from Baseline to Week 27 (%) n Median Q1, Q , , , , Collagen Type I Cross-linked C-telopeptide Change from Baseline to Week 12 (ng/l) n Median Q1, Q3-1285, , , , 570 Percent Change from Baseline to Week 12 (%) n Median Q1, Q , , , , Change from Baseline to Week 27 (ng/l) n Median Q1, Q3-1780, , , , 565 Percent Change from Baseline to Week 27 (%) n Median Q1, Q , , , , 23.52

10 etable 5. Summary of Low Corrected Calcium During the Study (N = 251) (N = 254) (N = 252) (N = 259) Number of patients with at least one post-baseline cca - N Number of patients with cca < 7.0 mg/dl 16 (6.4) 7 (2.8) 22 (8.8) 9 (3.5) Number of patients with cca < 7.5 mg/dl 39 (15.7) 4 (1.6) 58 (23.2) 8 (3.1) Number of patients with cca < 8.3 mg/dl 132 (53.0) 33 (13.0) 125 (50.0) 38 (14.7) N: patients who received at least one dose of investigational product. Percentages are based on N1. Categories are mutually exclusive. The lowest corrected calcium value of each patient is used.

11 etable 6. Treatment Emergent Adverse Events ( 1% in Arm in at Least One Study) in Descending Order of Frequency Preferred Term (N = 251) (N = 254) (N = 252) (N = 259) Number of patients reporting 230 (91.6) 200 (78.7) 231 (91.7) 210 (81.1) treatment-emergent adverse events Blood calcium decreased 153 (61.0) 21 (8.3) 168 (66.7) 31 (12.0) Muscle spasms 30 (12.0) 18 (7.1) 28 (11.1) 16 (6.2) Diarrhoea 18 (7.2) 18 (7.1) 36 (14.3) 26 (10.0) Nausea 31 (12.4) 13 (5.1) 23 (9.1) 19 (7.3) Vomiting 26 (10.4) 18 (7.1) 19 (7.5) 8 (3.1) Headache 18 (7.2) 20 (7.9) 20 (7.9) 11 (4.2) Hypocalcaemia 18 (7.2) 1 (0.4) 17 (6.7) 0 (0.0) Hypertension 12 (4.8) 17 (6.7) 19 (7.5) 12 (4.6) Hypotension 16 (6.4) 10 (3.9) 14 (5.6) 16 (6.2) Arteriovenous fistula site complication 13 (5.2) 14 (5.5) 16 (6.3) 12 (4.6) Dyspnoea 11 (4.4) 8 (3.1) 13 (5.2) 12 (4.6) Pain in extremity 17 (6.8) 11 (4.3) 7 (2.8) 9 (3.5) Paraesthesia 13 (5.2) 3 (1.2) 11 (4.4) 0 (0.0) Back pain 8 (3.2) 8 (3.1) 14 (5.6) 11 (4.2) Cough 12 (4.8) 7 (2.8) 10 (4.0) 15 (5.8) Hyperkalaemia 10 (4.0) 6 (2.4) 12 (4.8) 5 (1.9) Arthralgia 10 (4.0) 10 (3.9) 11 (4.4) 16 (6.2) Upper respiratory tract infection 8 (3.2) 10 (3.9) 13 (5.2) 16 (6.2) Urinary tract infection 12 (4.8) 4 (1.6) 9 (3.6) 6 (2.3) Pyrexia 12 (4.8) 11 (4.3) 8 (3.2) 9 (3.5) Anaemia 10 (4.0) 8 (3.1) 9 (3.6) 14 (5.4) Dizziness 8 (3.2) 7 (2.8) 10 (4.0) 6 (2.3) Nasopharyngitis 10 (4.0) 13 (5.1) 7 (2.8) 10 (3.9) Constipation 7 (2.8) 9 (3.5) 9 (3.6) 7 (2.7) Fluid overload 9 (3.6) 7 (2.8) 7 (2.8) 4 (1.5) Fall 3 (1.2) 5 (2.0) 12 (4.8) 9 (3.5) Bronchitis 7 (2.8) 4 (1.6) 7 (2.8) 4 (1.5) Decreased appetite 8 (3.2) 4 (1.6) 6 (2.4) 4 (1.5) Oropharyngeal pain 8 (3.2) 4 (1.6) 6 (2.4) 6 (2.3) Procedural hypotension 7 (2.8) 12 (4.7) 7 (2.8) 6 (2.3) Abdominal pain 8 (3.2) 7 (2.8) 5 (2.0) 8 (3.1) Angina pectoris 11 (4.4) 2 (0.8) 2 (0.8) 3 (1.2) Asthenia 8 (3.2) 6 (2.4) 5 (2.0) 9 (3.5) Cellulitis 3 (1.2) 3 (1.2) 10 (4.0) 7 (2.7) Dyspepsia 10 (4.0) 5 (2.0) 3 (1.2) 2 (0.8) Abdominal pain upper 8 (3.2) 8 (3.1) 4 (1.6) 6 (2.3)

12 etable 6. Treatment Emergent Adverse Events ( 1% in Arm in at Least One Study) in Descending Order of Frequency (continued) Preferred Term (N = 251) (N = 254) (N = 252) (N = 259) Anxiety 9 (3.6) 4 (1.6) 3 (1.2) 3 (1.2) Hypoglycaemia 6 (2.4) 6 (2.4) 6 (2.4) 9 (3.5) Vascular graft thrombosis 4 (1.6) 5 (2.0) 8 (3.2) 5 (1.9) Atrial fibrillation 7 (2.8) 5 (2.0) 4 (1.6) 5 (1.9) Fatigue 7 (2.8) 4 (1.6) 4 (1.6) 3 (1.2) Pain 6 (2.4) 1 (0.4) 5 (2.0) 3 (1.2) Pneumonia 6 (2.4) 5 (2.0) 5 (2.0) 12 (4.6) Non-cardiac chest pain 8 (3.2) 5 (2.0) 2 (0.8) 3 (1.2) Oedema peripheral 2 (0.8) 2 (0.8) 8 (3.2) 6 (2.3) Pruritus 6 (2.4) 5 (2.0) 4 (1.6) 6 (2.3) Arteriovenous fistula thrombosis 4 (1.6) 6 (2.4) 5 (2.0) 4 (1.5) Hyperphosphataemia 6 (2.4) 5 (2.0) 3 (1.2) 4 (1.5) Hypoaesthesia 3 (1.2) 3 (1.2) 6 (2.4) 1 (0.4) Malaise 6 (2.4) 3 (1.2) 3 (1.2) 3 (1.2) Musculoskeletal pain 6 (2.4) 3 (1.2) 3 (1.2) 7 (2.7) Sinusitis 6 (2.4) 1 (0.4) 3 (1.2) 0 (0.0) Vascular graft complication 6 (2.4) 0 (0.0) 3 (1.2) 4 (1.5) Blood calcium increased 1 (0.4) 0 (0.0) 7 (2.8) 1 (0.4) Cardiac failure congestive 5 (2.0) 2 (0.8) 3 (1.2) 4 (1.5) Epistaxis 4 (1.6) 1 (0.4) 4 (1.6) 1 (0.4) Insomnia 4 (1.6) 6 (2.4) 4 (1.6) 8 (3.1) Myalgia 4 (1.6) 1 (0.4) 4 (1.6) 0 (0.0) Chest pain 3 (1.2) 1 (0.4) 4 (1.6) 6 (2.3) Chills 3 (1.2) 4 (1.6) 4 (1.6) 2 (0.8) Contusion 2 (0.8) 4 (1.6) 5 (2.0) 2 (0.8) Hypercalcaemia 5 (2.0) 1 (0.4) 2 (0.8) 8 (3.1) Hypophosphataemia 2 (0.8) 1 (0.4) 5 (2.0) 0 (0.0) Muscular weakness 4 (1.6) 2 (0.8) 3 (1.2) 2 (0.8) Vascular access complication 5 (2.0) 1 (0.4) 2 (0.8) 6 (2.3) Venous stenosis 4 (1.6) 0 (0.0) 3 (1.2) 3 (1.2) Wound 3 (1.2) 2 (0.8) 4 (1.6) 5 (1.9) Arteriovenous fistula site infection 2 (0.8) 0 (0.0) 4 (1.6) 2 (0.8) Blood parathyroid hormone decreased 0 (0.0) 1 (0.4) 6 (2.4) 3 (1.2) Bradycardia 3 (1.2) 4 (1.6) 3 (1.2) 1 (0.4) Hyperglycaemia 3 (1.2) 3 (1.2) 3 (1.2) 2 (0.8) Metabolic acidosis 3 (1.2) 0 (0.0) 3 (1.2) 2 (0.8) Neck pain 2 (0.8) 5 (2.0) 4 (1.6) 4 (1.5)

13 etable 6. Treatment Emergent Adverse Events ( 1% in Arm in at Least One Study) in Descending Order of Frequency (continued) Preferred Term (N = 251) (N = 254) (N = 252) (N = 259) Tachycardia 2 (0.8) 2 (0.8) 4 (1.6) 8 (3.1) Toothache 3 (1.2) 3 (1.2) 3 (1.2) 1 (0.4) Abdominal discomfort 4 (1.6) 1 (0.4) 1 (0.4) 0 (0.0) Cataract 4 (1.6) 1 (0.4) 1 (0.4) 2 (0.8) Chronic obstructive pulmonary disease 3 (1.2) 2 (0.8) 2 (0.8) 2 (0.8) Depression 4 (1.6) 1 (0.4) 1 (0.4) 1 (0.4) Dysgeusia 3 (1.2) 2 (0.8) 2 (0.8) 1 (0.4) Gastroenteritis 2 (0.8) 0 (0.0) 3 (1.2) 4 (1.5) Gastrooesophageal reflux disease 4 (1.6) 1 (0.4) 1 (0.4) 2 (0.8) Haematuria 3 (1.2) 0 (0.0) 2 (0.8) 4 (1.5) Osteoarthritis 5 (2.0) 2 (0.8) 0 (0.0) 2 (0.8) Skin ulcer 3 (1.2) 2 (0.8) 2 (0.8) 3 (1.2) Supraventricular tachycardia 5 (2.0) 1 (0.4) 0 (0.0) 1 (0.4) Vertigo 3 (1.2) 2 (0.8) 2 (0.8) 6 (2.3) Arteriovenous fistula site haemorrhage 1 (0.4) 3 (1.2) 3 (1.2) 2 (0.8) Blood creatine phosphokinase increased 4 (1.6) 1 (0.4) 0 (0.0) 1 (0.4) Convulsion 1 (0.4) 2 (0.8) 3 (1.2) 2 (0.8) Coronary artery disease 3 (1.2) 2 (0.8) 1 (0.4) 1 (0.4) Device related infection 1 (0.4) 0 (0.0) 3 (1.2) 1 (0.4) Electrocardiogram QT prolonged 1 (0.4) 2 (0.8) 3 (1.2) 1 (0.4) Flank pain 3 (1.2) 0 (0.0) 1 (0.4) 1 (0.4) Haemorrhoids 1 (0.4) 1 (0.4) 3 (1.2) 0 (0.0) Limb injury 0 (0.0) 2 (0.8) 4 (1.6) 2 (0.8) Mental status changes 1 (0.4) 0 (0.0) 3 (1.2) 2 (0.8) Nasal congestion 3 (1.2) 0 (0.0) 1 (0.4) 1 (0.4) Neuropathy peripheral 1 (0.4) 2 (0.8) 3 (1.2) 1 (0.4) Osteomyelitis 3 (1.2) 1 (0.4) 1 (0.4) 3 (1.2) Procedural hypertension 3 (1.2) 0 (0.0) 1 (0.4) 0 (0.0) Pulmonary oedema 1 (0.4) 1 (0.4) 3 (1.2) 3 (1.2) Skin abrasion 1 (0.4) 3 (1.2) 3 (1.2) 1 (0.4) Thrombosis in device 3 (1.2) 2 (0.8) 1 (0.4) 2 (0.8) Abdominal distension 0 (0.0) 0 (0.0) 3 (1.2) 1 (0.4) Acute myocardial infarction 0 (0.0) 0 (0.0) 3 (1.2) 3 (1.2) Arteriovenous fistula site haematoma 3 (1.2) 1 (0.4) 0 (0.0) 2 (0.8) Chest discomfort 0 (0.0) 1 (0.4) 3 (1.2) 2 (0.8) Cholelithiasis 0 (0.0) 1 (0.4) 3 (1.2) 4 (1.5) Conjunctivitis 3 (1.2) 1 (0.4) 0 (0.0) 0 (0.0) Drug hypersensitivity 3 (1.2) 0 (0.0) 0 (0.0) 0 (0.0)

14 etable 6. Treatment Emergent Adverse Events ( 1% in Arm in at Least One Study) in Descending Order of Frequency (continued) Preferred Term (N = 251) (N = 254) (N = 252) (N = 259) Feeling hot 0 (0.0) 1 (0.4) 3 (1.2) 4 (1.5) Hepatic enzyme increased 0 (0.0) 0 (0.0) 3 (1.2) 0 (0.0) Peripheral swelling 0 (0.0) 2 (0.8) 3 (1.2) 2 (0.8) Respiratory distress 0 (0.0) 0 (0.0) 3 (1.2) 1 (0.4) Seasonal allergy 0 (0.0) 0 (0.0) 3 (1.2) 0 (0.0) N: patients who received at least one dose of investigational product

15 etable 7. Summary of Corrected QT Interval (Bazett and Fridericia) (N = 251) (N = 254) (N = 252) (N = 259) Corrected QT Interval QTc Bazett (msec) Baseline (59.4) 163 (64.2) 152 (60.3) 159 (61.4) > 450 to (23.5) 67 (26.4) 67 (26.6) 65 (25.1) > 480 to (6.8) 9 (3.5) 17 (6.7) 14 (5.4) > (3.2) 6 (2.4) 5 (2.0) 8 (3.1) Missing 18 (7.2) 9 (3.5) 11 (4.4) 13 (5.0) Maximum post-baseline (33.5) 126 (49.6) 79 (31.3) 124 (47.9) > 450 to (31.1) 88 (34.6) 103 (40.9) 82 (31.7) > 480 to (15.1) 18 (7.1) 36 (14.3) 24 (9.3) > (10.0) 11 (4.3) 22 (8.7) 17 (6.6) Missing 26 (10.4) 11 (4.3) 12 (4.8) 12 (4.6) Maximum increase from baseline (66.9) 221 (87.0) 177 (70.2) 218 (84.2) > 30 to (17.5) 17 (6.7) 54 (21.4) 24 (9.3) > 60 6 (2.4) 0 (0.0) 6 (2.4) 0 (0.0) Missing 33 (13.1) 16 (6.3) 15 (6.0) 17 (6.6)

16 etable 7. Summary of Corrected QT Interval (Bazett and Fridericia) (continued) (N = 251) (N = 254) (N = 252) (N = 259) Corrected QT Interval QTc Fridericia (msec) Baseline (71.3) 210 (82.7) 198 (78.6) 199 (76.8) > 450 to (18.3) 25 (9.8) 36 (14.3) 31 (12.0) > 480 to (2.4) 6 (2.4) 7 (2.8) 14 (5.4) > (0.8) 4 (1.6) 0 (0.0) 2 (0.8) Missing 18 (7.2) 9 (3.5) 11 (4.4) 13 (5.0) Maximum post-baseline (49.4) 177 (69.7) 134 (53.2) 172 (66.4) > 450 to (28.7) 49 (19.3) 72 (28.6) 53 (20.5) > 480 to (6.0) 13 (5.1) 23 (9.1) 15 (5.8) > (5.6) 4 (1.6) 11 (4.4) 7 (2.7) Missing 26 (10.4) 11 (4.3) 12 (4.8) 12 (4.6) Maximum increase from baseline (66.9) 222 (87.4) 180 (71.4) 227 (87.6) > 30 to (18.3) 16 (6.3) 54 (21.4) 15 (5.8) > 60 4 (1.6) 0 (0.0) 3 (1.2) 0 (0.0) Missing 33 (13.1) 16 (6.3) 15 (6.0) 17 (6.6) N: patients who received at least one dose of investigational product

17 efigure 1 A-B. Time to >30% Reduction From Baseline in PTH (Rolling Average of 3 PTH Values Were Used to Compare With Baseline) Each marker indicates the study week when patient(s) achieved >30% reduction in PTH (calculated as rolling average of the 3 most recent PTH values) relative to baseline. Number of patients at risk in each group was shown below the curves. All randomized patients were included.

18 efigure 2 A-B. Forest Plot for Difference in Proportion With >30% Decrease From Baseline in PTH Across Patient Subgroups

19 efigure 3 A-B. Use of Calcium Supplement or Calcium Containing Phosphate Binders Over Time Proportion of Patients (%) B Study Week n= n= Proportion of Patients (%) B Study Week n= n=

20 efigure 3 C-D. Use of Active Vitamin D Over Time Proportion of Patients (%) B Study Week n= n= Proportion of Patients (%) B Study Week n= n=

21 efigure 4 A-B. Mean PTH Value (pg/ml) (95% CI) by Study Week 1000 Mean PTH (pg/ml) Study Week n= n= Note: Week 27 was a post treatment visit Mean PTH (pg/ml) Study Week n= n= Note: Week 27 was a post treatment visit.