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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002854-11 | EudraCT Number |
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Octreotide capsule is a novel, orally-administered formulation of the commercially-available injectable drug octreotide. In a recent phase 3 trial (OPTMAL; NCT03252353), oral octreotide capsules demonstrated sustained biochemical response up to 13 months in patients with acromegaly previously managed with somatostatin analog injections (ref).
The objective of this study was to compare the efficacy, safety, and patient reported outcomes (PROs) between oral octreotide capsules and injectable somatostatin receptor ligands (SRLs).
This was phase 3, randomized, open-label, active controlled, multicenter study to evaluate the maintenance of response, safety and patient reported outcomes (PROs) in acromegaly patients treated with octreotide capsules and in patients treated with standard of care parenteral somatostatin receptor ligands (SRLs), who previously tolerated and demonstrated biochemical control on both treatments.
The core study consisted of three phases: a Screening phase, Run-in phase and a Randomized Controlled Treatment (RCT) phase.
Eligible patients who were biochemically controlled on parenteral SRLs were switched to octreotide capsules for a 26-week period Run-in phase. During this phase the effective dose for each patient was determined through dose titration.
Patients whose acromegaly has been controlled biochemically on octreotide capsules at the end of the Run-in phase entered a 36-week open-label RCT phase, where they randomized to continue on octreotide capsules or switch back to their injectable SRL treatment (as received prior to Screening).
Following the completion of the core study (Screening, Run-in and RCT phases), eligible patients were offered to enter the Study Extension phase and receive octreotide capsules until product marketing or study termination.
A Sub-study, performed in selected non-European sites, allowed patients with inadequate biochemical control on octreotide capsules during the Run-in phase to enter a Combination phase and receive co-administration of octreotide capsules with cabergoline tablets for a total of 36 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Run-in phase | Experimental | Oral octreotide capsules |
|
| RCT phase - Oral | Experimental | Oral octreotide capsules |
|
| RCT phase - Injectables | Active Comparator | Injectable somatostatin analogs (octreotide or lanreotide) |
|
| Combination phase (sub-study) | Experimental | Octreotide capsules plus cabergoline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octreotide capsules | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase | Proportion of patients who are biochemically controlled throughout the RCT phase. A patient was considered biochemically controlled if IGF-1 Time Weighted Average (TWA) during the RCT phase is <1.3 ULN | 62 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase | Proportion of patients with clinical and biochemical control at the end of the RCT phase. Patients were considered biochemically and clinically controlled if they met both of the following criteria:
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase | Proportion of patients reporting injection site reactions (ISRs). Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive ACRO-TSQ change scores indicate improvement while negative change scores indicate worsening. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maria Fleseriu, M.D., FACE | Northwest Pituitary Center, Oregon Health & Science University , Portland, OR, USA | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| Keck Medical Center of University of Southern California |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25664604 | Background | Melmed S, Popovic V, Bidlingmaier M, Mercado M, van der Lely AJ, Biermasz N, Bolanowski M, Coculescu M, Schopohl J, Racz K, Glaser B, Goth M, Greenman Y, Trainer P, Mezosi E, Shimon I, Giustina A, Korbonits M, Bronstein MD, Kleinberg D, Teichman S, Gliko-Kabir I, Mamluk R, Haviv A, Strasburger C. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708. doi: 10.1210/jc.2014-4113. Epub 2015 Feb 9. | |
| 26610414 |
| Label | URL |
|---|---|
| Click here for more information about Chiasma | View source |
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Prior to Run-in - all patients treated with SRLs (59.6% octreotide and 39.4% on lanreotide). 78.8% of patients were treated with medium to high doses of SRLs.
Prior to RCT - all patients were on oral octreotide capsules.
146 patients were enrolled into the Run-in phase. A total of 116 patients completed the Run-in phase and 30 patients discontinued the Run in phase.
Of the 116 patients who completed the Run-in phase, 92 patients with IGF-1<1.3 ULN entered the RCT phase, 11 patients with IGF-1≥1.3 and <2 ULN on the highest octreotide dose entered the Combination phase, and 13 patients did not continue treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Run-in Phase | Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day determined by individual dose titration |
| FG001 | RCT Phase - Oral |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Run-in Phase |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 16, 2020 | Aug 29, 2021 |
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| Week 62/ End of treatment; EOT |
| Proportion of Patients Who Maintain or Reduce the Overall Number of Active Acromegaly Symptoms at the End of the RCT Phase | Proportion of patients who maintain or reduce the overall number of active acromegaly symptoms at the end of the RCT phase (week 62/ EOT) , compared to week 26 (start of the RCT phase | 62 weeks |
| Proportion of Patients Who Maintain or Improve Their Overall Acromegaly Index of Severity (AIS) Score at the End of the RCT Phase | Proportion of patients who maintain or improve their overall Acromegaly index of severity (AIS) score at the end of the RCT phase (improvement defined as a reduction of at least one point in the AIS score), compared to week 26 (start of the RCT phase) | 62 weeks |
| Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase | Proportion of patients of those completing the RCT phase (at a time octreotide capsules were not commercially available at the specific country), who entered the Study Extension phase, overall and by treatment group | 62 weeks |
| Change in IGF-1 Levels in the RCT Phase | Change in IGF-1 levels from the start of the randomized phase to the end of RCT phase. Complete Responder (CR) is defined as IGF-1 ≤ 1 x ULN; Partial Responder (PR) is defined as 1 x ULN < IGF-1 < 1.3 x ULN, and Non-Responder (NR): IGF-1 ≥ 1.3 x ULN | Change from Week 26 to week 62 |
| Change in GH Levels in the RCT Phase | Change in GH levels from the start of the randomized phase through the end of RCT phase. | Change from Week 26 to week 62 |
| 62 weeks |
| Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase | Proportion of patients reporting interference with daily activities in the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) during the RCT phase. Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening. | 62 weeks |
| Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis | Proportion of patients on octreotide capsules who are biochemically controlled at the end of the RCT phase defined as IGF-1< 1.3 x ULN based on average of weeks 58 and 62 | Average of weeks 58 and 62 |
| Proportion of Week 26 Responders on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Sensitivity Analysis | Proportion of patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark sensitivity analysis- Week 26 responders | 62 weeks |
| Proportion of Patients Biochemically Controlled at the End of Run-in | Proportion of patients biochemically controlled at the end of the Run-in phase, defined as average IGF-1 levels during weeks 24 and 26 < 1.3xULN | 26 weeks |
| Proportion of Patients With a Reduction in the Overall Number of Active Acromegaly Symptoms at the End of the Run-in Phase | Proportion of patients with a reduction in the overall number of active acromegaly symptoms at the end of the Run-in phase compared to Baseline | 26 weeks |
| Proportion of Patients With Improved Acromegaly Index of Severity (AIS) Score at the End of the Run-in Phase | Proportion of patients with improved AIS score at the end of the Run-in phase compared to Baseline Acromegaly index of severity (AIS) at the end of Run-in phase compared to Baseline. The Acromegaly Index of Severity (AIS) symptom score is calculated based on the presence and severity of 5 acromegaly signs/symptoms: headache, swelling of extremities, joint pain, sweating, and fatigue. Each symptom was graded from no symptoms (score 0), to mild symptoms (1), moderate (2), or severe symptoms (3). | 26 weeks |
| EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Index Scores During the Run-in Phase | Change from baselines in EQ-5D-5L Index scores in randomized participants during the Run-in phase. EQ-5D-5L (five severity levels EQ-5D) is a standardized instrument completed by the patient for use as a measure of health outcome applicable to a wide range of health conditions. It comprises 5 dimensions of health: mobility, ability to self care, ability to undertake usual activities, pain and discomfort, and anxiety and depression. Based on qualitative and quantitative studies conducted by the EuroQol Group, there are 5 levels under each domain: 'no problems' (assigned a value of 1), 'slight problems' (assigned a value of 2), 'moderate problems' (assigned a value of 3), 'severe problems' (assigned a value of 4), and 'unable to/extreme problems' (assigned a value of 5). An EQ-5D Index score is calculated based on the responses to these 5 dimensions of health. Weights for use in the index calculation are not universally available. Higher values represent better health states. | 26 weeks |
| Change From Baseline to End of RCT Phase in WPAI | Work Productivity and Activity Impairment Questionnaire- RCT phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity. The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes). | 26 weeks |
| Change From Baseline to End of Run-in Phase in WPAI | Work Productivity and Activity Impairment Questionnaire- Run-in phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity. The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes). | 62 weeks |
| Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. | Change in Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) PRO questionnaire from baseline to end of Run-in phase in randomized patients. Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening. | 26 weeks |
| Los Angeles |
| California |
| 90033 |
| United States |
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
| Emory University | Atlanta | Georgia | 30322 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| John H. Stroger, Jr. Hospital of Cook County | Chicago | Illinois | 60612 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Rutgers - Robert Wood Johnson Medical School | New Brunswick | New Jersey | 08903 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| The Ohio State University Wexner Medical Center | Columbus | Ohio | 43203 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| Allegheny Endocrinology Associates | Pittsburgh | Pennsylvania | 15212 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Houston Methodist Research Institute | Houston | Texas | 77030 | United States |
| Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie | Graz | A-8036 | Austria |
| Medizinische Universität Wien | Vienna | A-1090 | Austria |
| Hospices Civils de Lyon | Bron | 69677 | France |
| Hôpital Bicêtre APHP | Le Kremlin-Bicêtre | 94275 | France |
| Praxis für Endokrinologie und Diabetologie Dr M Droste | Oldenburg | 26122 | Germany |
| Magyar Honvedseg Egeszsegugyi Kozpont | Budapest | H-1062 | Hungary |
| University of Pecs | Pécs | H-7624 | Hungary |
| Szegedi Tudományegyetem, I. Belgyógyászati Klinika | Szeged | H-6720 | Hungary |
| Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia | Monserrato | 09042 | Italy |
| Università di Pisa Dipartimento di Medicina Clinica e Sperimentale | Pisa | 56124 | Italy |
| Fondazione Policlinico Universitario A. Gemelli Università Cattolica del S.Cuore S.C. Endocrinologia e Malattie del Metabolismo | Rome | 00168 | Italy |
| Hospital of LUHS Kauno Klinikos | Kaunas | LT-50009 | Lithuania |
| Vaidotas Urbanavicius Individuali ImonÄ— | Vilnius | LT-10207 | Lithuania |
| Katedra i Klinika Endokrynologii i Chorob Wewnetrznych Gdanski Uniwersytet Medyczny | Gdansk | 80-211 | Poland |
| Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami | Wroclaw | 50-367 | Poland |
| "C.I. Parhon" National Institute of Endocrinology I Clinical Endocrinology Department - Endemic goitier and its complications | Bucharest | 011863 | Romania |
| Antrium Multidisciplinary Medical Clinic | Barnaul | 656043 | Russia |
| Interregional Clinical Diagnostic Center | Kazan' | 420101 | Russia |
| Regional State Budgetary Healthcare Institution Regional State Hospital | Krasnoyarsk | 660022 | Russia |
| Sechenov Moscow First State Medical University | Moscow | 119881 | Russia |
| "Atlas" Medical Center | Moscow | 121170 | Russia |
| Vladimirsky Moscow Regional Research Clinical Institute | Moscow | 129110 | Russia |
| Novosibirsk State Regional Clinical Hospital | Novosibirsk | 630087 | Russia |
| Federal State Budgetary Institution "V. A. Almazov Federal North-West Medical Research Centre" of the Ministry of Health of the Russian Federation | Saint Petersburg | 194156 | Russia |
| "Centre Diabetes" LLC | Samara | 443041 | Russia |
| Clinical Centre of Serbia, Clinic for Endocrinology Diabetes and Metabolic Diseases | Belgrade | 11 000 | Serbia |
| Hospital Universitario de la Ribera | Alzira | 46600 | Spain |
| Hospital Universitari Germans Trias i Pujol | Barcelona | 08916 | Spain |
| Hospital General Universitario Gregorio Maranon | Madrid | 28007 | Spain |
| Complejo Hospitalario Universitario de Santiago de Compostela | Santiago de Compostela | 15706 | Spain |
| Campus Del Hospital Universitario Virgen del Rocio | Seville | 46013 | Spain |
| University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital | Birmingham | B15 2GW | United Kingdom |
| Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary | Manchester | M13 9WL | United Kingdom |
| Royal Victoria Infirmary | Newcastle upon Tyne | NE1 4LP | United Kingdom |
| Royal Hallamshire Hospital | Sheffield | S10 2JF | United Kingdom |
| Background |
| Melmed S. New therapeutic agents for acromegaly. Nat Rev Endocrinol. 2016 Feb;12(2):90-8. doi: 10.1038/nrendo.2015.196. Epub 2015 Nov 27. |
| 34953531 | Derived | Fleseriu M, Dreval A, Bondar I, Vagapova G, Macut D, Pokramovich YG, Molitch ME, Leonova N, Raverot G, Grineva E, Poteshkin YE, Gilgun-Sherki Y, Ludlam WH, Patou G, Haviv A, Gordon MB, Biermasz NR, Melmed S, Strasburger CJ. Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2022 Feb;10(2):102-111. doi: 10.1016/S2213-8587(21)00296-5. Epub 2021 Dec 22. |
Oral octreotide capsules
Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day
| FG002 | RCT Phase - Injectables | Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide- 10, 20, 30, 40 mg. Lanreotide- 60, 90, 120mg. |
| FG003 | Combination Phase (Sub-study) | Octreotide capsules plus cabergoline Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day Cabergoline: Cabergoline - Up to 3.5mg/week |
| COMPLETED |
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| NOT COMPLETED |
|
| RCT Phase |
|
| Combination Phase |
|
Acromegaly patients who previously tolerated and demonstrated a biochemical control on SRLs
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| ID | Title | Description |
|---|---|---|
| BG000 | Run-in Phase | Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day |
| BG001 | RCT Phase - Oral | Oral octreotide capsules Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day |
| BG002 | RCT Phase - Injectables | Injectable somatostatin analogs (octreotide or lanreotide) Injectable Somatostatin Analogs (octreotide or lanreotide): Octreotide - 10, 20, 30mg. Lanreotide 60,90, 120mg. |
| BG003 | Combination Phase (Sub-study) | Octreotide capsules plus cabergoline Octreotide capsules: Octreotide capsules 40mg/day, 60mg/day, 80mg/day Cabergoline: Cabergoline - 3.5mg/week |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Number of participants was breakdown per study phase. | Count of Participants | Participants |
| ||||||||||
| Age, Continuous | Number of participants was breakdown per study phase. | Mean | Standard Deviation | years |
| |||||||||
| Sex: Female, Male | Number of participants was breakdown per study phase. | Count of Participants | Participants |
| ||||||||||
| Ethnicity (NIH/OMB) | Number of participants was breakdown per study phase. | Count of Participants | Participants |
| ||||||||||
| Race (NIH/OMB) | Number of participants was breakdown per study phase. | Count of Participants | Participants |
| ||||||||||
| Region of Enrollment | Region of enrollment in the Run-in phase. | Region of enrollment was summarized in the Run-in phase only, where 146 were randomized. | Count of Participants | Participants |
| |||||||||
| Region of Enrollment | Region of enrollment in the RCT phase. | Region of enrollment was captured for the RCT phase only, where patients were randomized to either oral octreotide (55) or injectable SRLs (37) . | Count of Participants | Participants |
| |||||||||
| Region of Enrollment | Region of enrollment- Combination phase | Region of enrollment was only captured for the Combination phase sub-study, in which 14 patients were included. . | Count of Participants | Participants |
| |||||||||
| IGF-1 levels | IGF-1 levels normalized for age and gender. The upper limit of normal is 1.0 x ULN | Mean calculated is phase-specific. | Mean | Standard Deviation | X Upper limit of normal (ULN) |
| ||||||||
| IGF-I categorical | Number calculated is phase-specific. | Count of Participants | Participants |
| ||||||||||
| GH | Data analyzed in study-specific. | Mean | Standard Deviation | ng/ mL |
| |||||||||
| Acromegaly Index of Severity (AIS) symptom score | The Acromegaly Index of Severity (AIS) symptom score is calculated based on the presence and severity of 5 acromegaly signs/symptoms: headache, swelling of extremities, joint pain, sweating, and fatigue. Each symptom was graded from no symptoms (score 0), to mild symptoms (1), moderate (2), or severe symptoms (3). The minimal total score is 0 and the maximal is 15. | Analysis performed is phase-specific. | Mean | Standard Deviation | units on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase | Proportion of patients who are biochemically controlled throughout the RCT phase. A patient was considered biochemically controlled if IGF-1 Time Weighted Average (TWA) during the RCT phase is <1.3 ULN | Posted | Count of Participants | Participants | 62 weeks |
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| Secondary | Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase | Proportion of patients with clinical and biochemical control at the end of the RCT phase. Patients were considered biochemically and clinically controlled if they met both of the following criteria:
| Posted | Count of Participants | Participants | Week 62/ End of treatment; EOT |
|
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| Secondary | Proportion of Patients Who Maintain or Reduce the Overall Number of Active Acromegaly Symptoms at the End of the RCT Phase | Proportion of patients who maintain or reduce the overall number of active acromegaly symptoms at the end of the RCT phase (week 62/ EOT) , compared to week 26 (start of the RCT phase | Posted | Count of Participants | Participants | 62 weeks |
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| Secondary | Proportion of Patients Who Maintain or Improve Their Overall Acromegaly Index of Severity (AIS) Score at the End of the RCT Phase | Proportion of patients who maintain or improve their overall Acromegaly index of severity (AIS) score at the end of the RCT phase (improvement defined as a reduction of at least one point in the AIS score), compared to week 26 (start of the RCT phase) | Posted | Count of Participants | Participants | 62 weeks |
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| Secondary | Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase | Proportion of patients of those completing the RCT phase (at a time octreotide capsules were not commercially available at the specific country), who entered the Study Extension phase, overall and by treatment group | Posted | Count of Participants | Participants | 62 weeks |
|
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| Secondary | Change in IGF-1 Levels in the RCT Phase | Change in IGF-1 levels from the start of the randomized phase to the end of RCT phase. Complete Responder (CR) is defined as IGF-1 ≤ 1 x ULN; Partial Responder (PR) is defined as 1 x ULN < IGF-1 < 1.3 x ULN, and Non-Responder (NR): IGF-1 ≥ 1.3 x ULN | Posted | Mean | Standard Deviation | x Upper limit of normal ("ULN") | Change from Week 26 to week 62 |
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| Secondary | Change in GH Levels in the RCT Phase | Change in GH levels from the start of the randomized phase through the end of RCT phase. | Posted | Mean | Standard Deviation | ng/mL | Change from Week 26 to week 62 |
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| Other Pre-specified | Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase | Proportion of patients reporting injection site reactions (ISRs). Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive ACRO-TSQ change scores indicate improvement while negative change scores indicate worsening. | Posted | Count of Participants | Participants | 62 weeks |
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| Other Pre-specified | Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase | Proportion of patients reporting interference with daily activities in the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) during the RCT phase. Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening. | Posted | Count of Participants | Participants | 62 weeks |
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| Other Pre-specified | Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis | Proportion of patients on octreotide capsules who are biochemically controlled at the end of the RCT phase defined as IGF-1< 1.3 x ULN based on average of weeks 58 and 62 | Posted | Count of Participants | Participants | Average of weeks 58 and 62 |
|
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| Other Pre-specified | Proportion of Week 26 Responders on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Sensitivity Analysis | Proportion of patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark sensitivity analysis- Week 26 responders | Posted | Count of Participants | Participants | 62 weeks |
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| Other Pre-specified | Proportion of Patients Biochemically Controlled at the End of Run-in | Proportion of patients biochemically controlled at the end of the Run-in phase, defined as average IGF-1 levels during weeks 24 and 26 < 1.3xULN | Posted | Count of Participants | Participants | 26 weeks |
|
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| Other Pre-specified | Proportion of Patients With a Reduction in the Overall Number of Active Acromegaly Symptoms at the End of the Run-in Phase | Proportion of patients with a reduction in the overall number of active acromegaly symptoms at the end of the Run-in phase compared to Baseline | Posted | Count of Participants | Participants | 26 weeks |
|
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| Other Pre-specified | Proportion of Patients With Improved Acromegaly Index of Severity (AIS) Score at the End of the Run-in Phase | Proportion of patients with improved AIS score at the end of the Run-in phase compared to Baseline Acromegaly index of severity (AIS) at the end of Run-in phase compared to Baseline. The Acromegaly Index of Severity (AIS) symptom score is calculated based on the presence and severity of 5 acromegaly signs/symptoms: headache, swelling of extremities, joint pain, sweating, and fatigue. Each symptom was graded from no symptoms (score 0), to mild symptoms (1), moderate (2), or severe symptoms (3). | Posted | Count of Participants | Participants | 26 weeks |
|
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| Other Pre-specified | EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Index Scores During the Run-in Phase | Change from baselines in EQ-5D-5L Index scores in randomized participants during the Run-in phase. EQ-5D-5L (five severity levels EQ-5D) is a standardized instrument completed by the patient for use as a measure of health outcome applicable to a wide range of health conditions. It comprises 5 dimensions of health: mobility, ability to self care, ability to undertake usual activities, pain and discomfort, and anxiety and depression. Based on qualitative and quantitative studies conducted by the EuroQol Group, there are 5 levels under each domain: 'no problems' (assigned a value of 1), 'slight problems' (assigned a value of 2), 'moderate problems' (assigned a value of 3), 'severe problems' (assigned a value of 4), and 'unable to/extreme problems' (assigned a value of 5). An EQ-5D Index score is calculated based on the responses to these 5 dimensions of health. Weights for use in the index calculation are not universally available. Higher values represent better health states. | All patients who were randomized to the RCT phase | Posted | Mean | 95% Confidence Interval | units on a scale | 26 weeks |
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| Other Pre-specified | Change From Baseline to End of RCT Phase in WPAI | Work Productivity and Activity Impairment Questionnaire- RCT phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity. The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes). | Posted | Least Squares Mean | 95% Confidence Interval | Percentage change from Baseline RCT | 26 weeks |
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| Other Pre-specified | Change From Baseline to End of Run-in Phase in WPAI | Work Productivity and Activity Impairment Questionnaire- Run-in phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity. The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes). | Posted | Least Squares Mean | 95% Confidence Interval | Percentage change from Run-in baseline | 62 weeks |
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| Other Pre-specified | Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. | Change in Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) PRO questionnaire from baseline to end of Run-in phase in randomized patients. Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening. | Change in Acro-TSQ domains in randomized patients | Posted | Mean | 95% Confidence Interval | score on a scale | 26 weeks |
|
|
1 year, 3 months for both the Run-in and RCT phases.
Safety population: All participants enrolled in the study who received any amount of the study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Run-in Phase | Oral octreotide capsules Octreotide capsules | 0 | 146 | 6 | 146 | 106 | 146 |
| EG001 | RCT Phase - Oral | Oral octreotide capsules Octreotide capsules | 1 | 55 | 3 | 55 | 39 | 55 |
| EG002 | RCT Phase - Injectables | Injectable somatostatin analogs (octreotide or lanreotide) Octreotide capsules | 0 | 37 | 3 | 37 | 26 | 37 |
| EG003 | Combination Phase (Sub-study) | Octreotide capsules plus cabergoline Octreotide capsules | 0 | 14 | 0 | 14 | 11 | 14 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial flutter | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Post cholecystectomy syndrome | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pancreatitis acute | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal distention | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Injection site nodule | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Extrasystoles | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Hepatic cyst | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hepatic steatosis | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Influnza | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Asi Haviv, VP Clinical development | Amryt | 972 8 9393888 | Asi@amrytpharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 15, 2019 | Aug 29, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000172 | Acromegaly |
| ID | Term |
|---|---|
| D001849 | Bone Diseases, Endocrine |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D006964 | Hyperpituitarism |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D015282 | Octreotide |
| ID | Term |
|---|---|
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
|
| RCT phase |
|
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| Combination Phase |
|
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| RCT phase |
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| Combination phase |
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| RCT phase |
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| Combination phase |
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| RCT phase |
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| Combination phase |
|
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| RCT phase |
|
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| Combination phase |
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| United States |
|
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| Spain |
|
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| Russia |
|
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| Austria |
|
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| Italy |
|
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| France |
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| Lithuania |
|
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| Serbia |
|
|
| Germany |
|
|
|
| United States |
|
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| Spain |
|
|
| Russia |
|
|
| Austria |
|
|
| Italy |
|
|
| France |
|
|
| Lithuania |
|
|
| Serbia |
|
|
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| Russia |
|
|
| Serbia |
|
|
|
| RCT phase |
|
|
| Combination phase |
|
|
|
| Run-in phase- > 1 to < 1.3 ULN |
|
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| Run-in phase- ≥ 1.3 ULN |
|
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| RCT phase- ≤ 1 ULN |
|
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| RCT phase- > 1 to < 1.3 ULN |
|
|
| RCT phase- ≥ 1.3 ULN |
|
|
| Combination phase- ≤ 1 ULN |
|
|
| Combination phase- > 1 to < 1.3 ULN |
|
|
| Combination phase- ≥ 1.3 ULN |
|
|
|
| RCT phase |
|
|
| Combination phase |
|
|
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| RCT phase |
|
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| Combination phase |
|
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| Units | Counts |
|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Title | Denominators | Categories |
|---|
|
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
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| Units | Counts |
|---|---|
| Participants |
|
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|
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| Between 18 and 65 years |
|
| >=65 years |
|
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|