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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-005888-52 | EudraCT Number |
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| Name | Class |
|---|---|
| Nimbus Lakshmi, Inc. | INDUSTRY |
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This study is designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in participants with active Psoriatic Arthritis (PsA).
This is a Phase 2b, Randomized, Multi-center, Double-Blind, Placebo-Controlled, Multiple Dose Study.
Randomization to one of the treatments with NDI-034858 Dose 1, 2, 3 or placebo once daily (QD) will be based on a 1:1:1:1 scheme.
The maximum study duration per participant is approximately 20 weeks, including up to 30 days for the screening period, a 12-week treatment period, and a 4-week safety follow-up period.
Efficacy will be assessed using the ACR20 composite measure (including tender and swollen joint count, patient assessment of PsA pain visual analog scale (VAS), patient global PsA assessment VAS, physician global PsA assessment, HAQ-DI, and hsCRP) as well as the additional components. Efficacy for psoriasis among participants who have ≥ 3% BSA) involvement on Day 1, will be measured using PASI, PGAs, and BSA.
Safety will be assessed by collecting AEs, recording vital signs, performing physical examinations, and evaluating clinical laboratory and ECGs results.
Blood samples will be collected to measure plasma concentrations of NDI-034858.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received placebo capsules, orally, QD for 12 weeks. |
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| NDI-034858 Low Dose | Experimental | Participants received NDI-034858 low dose, capsules, orally, QD for 12 weeks. |
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| NDI-034858 Medium Dose | Experimental | Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
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| NDI-034858 High Dose | Experimental | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NDI-034858 | Drug | NDI-034858 oral capsule |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | ACR20 is composite measure defined as improvement of 20 percent(%) from baseline in both number of tender (68) & number of swollen (66) joints & a 20% improvement in at least 3 of following 5 criteria: patient global assessment of psoriatic arthritis (PGA-PsA) [visual analog scale (VAS) where, 0=very good, no symptoms & 100=very poor, severe symptoms], physician global assessment of psoriatic arthritis (PhGA-PsA) [(VAS) where 0=no disease activity & 100=maximum disease activity], patient global assessment of psoriatic arthritis pain (PGAAP) [(VAS) where 0=no pain & 100=most severe pain], disability history questionnaire i.e., Health Assessment Questionnaire-Disability Index [HAQ-DI] (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip & activities, 0=without difficulty to 3=unable to do) & acute phase reactant like high sensitivity C-reactive protein [hsCRP]). Percentages are rounded off to the nearest decimal. | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | The ACR-50 is a composite measure defined as improvement of 50% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 50% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA [(VAS) where 0=no disease activity and 100=maximum disease activity], PGAAP [(VAS) where 0=no pain & 100=most severe pain], disability history questionnaire (i.e., HAQ-DI) [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do] and an acute phase reactant [i.e., erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)]. Percentages are rounded off to the nearest decimal. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nimbus site #XYZ | Palm Desert | California | 92260 | United States | ||
| Nimbus site #XYZ |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
A total of 305 participants with a diagnosis of psoriatic arthritis were enrolled in a 1:1:1:1 ratio to receive either one of the 3 doses of NDI-034858 or placebo.
Participants took part in the study at 45 investigative sites in the United States (US), Germany, Poland, and the Czech Republic from 6 January 2022 to 2 June 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo capsules, orally, once daily (QD) for 12 weeks. |
| FG001 | NDI-034858 Low Dose | Participants received NDI-034858 low dose, capsules, orally, QD for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 | May 5, 2023 | May 3, 2024 |
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Treatment and randomization information will be kept confidential and will not be released to the investigator, the study staff, the contract research organization (CRO), or the sponsor's study team until after the conclusion of the study.
| Placebo | Other | NDI-034858-matching oral placebo capsule |
|
| Week 12 |
| Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | The ACR-70 is a composite measure defined as improvement of 70% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 70% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA [(VAS) where 0=no disease activity and 100=maximum disease activity], PGAAP [(VAS) where 0=no pain & 100=most severe pain], disability history questionnaire (i.e., HAQ-DI) [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do] and an acute phase reactant (i.e., ESR or CRP). Percentages are rounded off to the nearest decimal. | Week 12 |
| Change From Baseline in Tender Joint Count (TJC) at Week 12 | The TJC 68 is a total score of points assigned for the presence of tenderness in the 68 joints in the upper body and upper/lower extremity. The response to tenderness for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all tender joints was derived. The overall tender joint count ranged from 0 to 68, with a higher score indicating a greater degree of tenderness. A negative change from baseline indicates improvement. | Baseline, Week 12 |
| Change From Baseline in Swollen Joint Count (SJC) at Week 12 | The SJC 66 (TJC 68 joint assessment minus hip joints, which cannot be assessed for swelling) is a total score of points assigned for presence of swelling in the 66 joints in the upper body and upper/lower extremity. The response to swelling for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all swollen joints was derived. The overall swollen joint count ranged from 0 to 66, with a higher score indicating a greater degree of swelling. A negative change from baseline indicates improvement. | Baseline, Week 12 |
| Change From Baseline in PGA-PsA at Week 12 | Participants assessed their overall disease status based on symptoms of psoriasis and psoriatic arthritis at the time of the visit using the PGA-PsA VAS of 100 millimeters (mm) which ranges from 0 (very good, no symptoms) to 100 (very poor, severe symptoms). A negative change from Baseline indicates improvement in symptoms. | Baseline, Week 12 |
| Change From Baseline in PGAAP at Week 12 | Participants assessed their overall psoriatic arthritis-related pain at the time of the visit using the PGAAP VAS of 100 mm which ranges from 0 (no pain) to 100 (most severe pain). A negative change from Baseline indicates improvement in pain. | Baseline, Week 12 |
| Change From Baseline in PhGA-PsA at Week 12 | The participants' overall disease status was assessed, taking into account signs, symptoms, and function, of all components of joint and skin affected at the time of the visit and this overall status was rated by the investigator using the PhGA-PsA VAS of 100 mm where 0 is 'very good, asymptomatic, and no limitation of normal activities' and 100 is 'very poor, very severe symptoms which are intolerable, and inability to carry out all normal activities'. A negative change from Baseline indicates improvement in symptoms. | Baseline, Week 12 |
| Change From Baseline in HAQ-DI Total Score at Week 12 | The HAQ-DI consists of 20 questions referring to eight domains consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored from 0 (without any difficulty) to 3 (unable to do). The worst score within each domain will be used as the domain score (i.e., if the score for one question is 1 and 2 for the other, then the worst score for the domain is 2). The HAQ-DI total score is calculated by dividing the sum of the domain scores by the number of non-missing domains. The total score indicates the patient's self-assessed level of functional ability and higher scores indicate worse functional ability. The HAQ-DI total score ranges from 0 to 3. A higher score indicates worse function and greater disability. A negative change from Baseline indicates improved function. | Baseline, Week 12 |
| Change From Baseline in Dactylitis Count (DC) at Week 12 | Tender score (0 = no tenderness, 1 = tender, 2 = tender and wince, 3 = tender and withdraw) is collected for Dactylitis Assessments on the Dactylitis Score Sheet that is used for calculation of total score. DC equals the number of tender fingers and toes (tender score >0). For participants with dactylitis status absent for all the fingers and toes, the DC is set as 0. The total score range of DC is from 0 to 60, higher scores indicate greater presence of dactylitis. A negative change from baseline indicates improvement. | Baseline, Week 12 |
| Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | Enthesitis is assessed using LEI. The enthesitis examination by LEI evaluates the presence or absence of pain by applying local pressure on 6 anatomical sites: medial femoral condyle (left and right), lateral epicondyle (left and right), and the achilles tendon insertion (left and right). Enthesitis at each site is scored as 0 (enthesitis absent) and 1 (enthesitis present). LEI is derived as the sum of the enthesitis score over the 6 sites, divided by the number of sites with non-missing score. The total score ranges from 0 to 6, higher scores indicate greater degree of enthesitis. A negative change from baseline indicates improvement. | Baseline, Week 12 |
| Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | MDA is a measure to indicate a state of minimal disease activity, and is a composite score of 7 domains. A participant is considered as having achieved the MDA if the participant fulfills at least 5 of the following 7 criteria: TJC 68 ≤1; SJC 66 ≤1; Psoriasis area and severity index (PASI) score ≤1 [The total score ranges from 0 (no disease) to 72 (maximal disease)] or body surface area (BSA) ≤3%; PGAAP ≤15 [using VAS on a scale of 0 (no pain) to 100 (serious pain)]; PGA-PsA ≤20 [using VAS on a scale of 0 (very well) to 100 (very poor)]; HAQ-DI score ≤0.5; LEI score ≤1. Percentages are rounded off to the nearest decimal. | Week 12 |
| Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | The DAPSA score is a composite score and was calculated using: TJC68, SJC66, PGA-PsA, PGAAP, and hsCRP level (milligram per deciliter [mg/dL]). DAPSA scores 0-4 = remission, 5-14 = low disease activity, 15-28 = moderate disease activity, and >28 = high disease activity. The DAPSA score has a lower bound of 0 and has no upper bound. A higher DAPSA score indicated more active disease activity. A negative change from baseline indicates improvement. | Baseline, Week 12 |
| Percentage of Participants Who Achieved PASI-75 Response at Week 12 | PASI-75 is assessed in participants with psoriasis involvement for ≥ 3% of the BSA at Baseline and assesses the extent of involvement and severity of psoriasis. To calculate the PASI, the body is divided into 4 regions: the head and neck, trunk, upper limbs, and lower limbs. Each of these areas are assessed separately for the percentage of the area involved and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90% to 100% involvement). The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). For PASI-75, the improvement threshold from baseline in PASI score is 75%. A higher score indicates more severe disease. Percentages are rounded off to the nearest decimal. | Week 12 |
| Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | PhGA-PsO responder is defined as participants 1) who had PhGA-PsO score of 0 or 1 at any given post-baseline visit; and 2) who had at least 2-point improvement from baseline. The PhGA-PsO is measured using a 0 to 4 scale with a 0 meaning clear or a 4 meaning severe. The proportion of participants achieving PhGA-PsO response at Week 12 was calculated and analyzed for participants with a score of at least 2 at baseline. Percentages are rounded off to the nearest decimal. | Week 12 |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Adverse Event(AE)=medical occurrence that does not necessarily have a causal relationship with this drug also including clinically meaningful findings in laboratory safety tests,vital signs,weight,and electrocardiogram(ECG).TEAEs=AEs occurring at time of or post study drug dosing until study end.SAE=any medical occurrence at any dose that resulted in death,was life-threatening,required inpatient hospitalization/prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was a congenital abnormality/birth defect,an important medical event.AESIs included Common Terminology Criteria for Adverse Events(CTCAE)Grade≥2 cytopenia,CTCAE Grade≥3 elevation of creatine phosphokinase(CPK)[clinically significant or not]defined as CPK>5xupper limit of normal(ULN),infections,adverse events of abnormal liver function tests,adverse events of renal dysfunction,major adverse cardiovascular events,thromboembolic events,gastrointestinal perforation,and malignancies. | From first dose of study drug up to end of study (up to Week 16) |
| Plasma Concentration of NDI-034858 | Plasma concentration of NDI-034858 was measured in participants who received low, medium, or high doses of NDI-034858. | Pre-dose, 1 hour post-dose on Day 1 and Week 4, 4 hours post-dose at Week 4, Pre-dose at Week 8, and anytime at Week 12 |
| Upland |
| California |
| 91786 |
| United States |
| Nimbus site #XYZ | Hollywood | Florida | 33024 | United States |
| Nimbus site #XYZ | Plantation | Florida | 33324 | United States |
| Nimbus site #XYZ | St. Petersburg | Florida | 33705 | United States |
| Nimbus site #XYZ | Tampa | Florida | 33613 | United States |
| Nimbus site #XYZ | Tampa | Florida | 33614 | United States |
| Nimbus site #XYZ | Winter Park | Florida | 32789 | United States |
| Nimbus site #XYZ | Zephyrhills | Florida | 33542 | United States |
| Nimbus site #XYZ | Indianapolis | Indiana | 46250 | United States |
| Nimbus site #XYZ | West Des Moines | Iowa | 50265 | United States |
| Nimbus site #XYZ | Lake Charles | Louisiana | 70605 | United States |
| Nimbus site #XYZ | Worcester | Massachusetts | 01605 | United States |
| Nimbus site #XYZ | Albuquerque | New Mexico | 87102 | United States |
| Nimbus site #XYZ | Charlotte | North Carolina | 28210 | United States |
| Nimbus site #XYZ | Duncansville | Pennsylvania | 16635 | United States |
| Nimbus site #XYZ | Columbia | South Carolina | 29204 | United States |
| Nimbus site #XYZ | Jackson | Tennessee | 38305 | United States |
| Nimbus site #XYZ | Baytown | Texas | 77521 | United States |
| Nimbus site #XYZ | Corpus Christi | Texas | 78404 | United States |
| Nimbus site #XYZ | Houston | Texas | 77089 | United States |
| Nimbus site #XYZ | Mesquite | Texas | 75150 | United States |
| Nimbus site #XYZ | Beckley | West Virginia | 25801 | United States |
| Nimbus site #XYZ | Hlučín | Ostrava-město | 748 01 | Czechia |
| Nimbus site #XYZ | Prague | Praha 3 | 130 00 | Czechia |
| Nimbus site #XYZ | Ostrava | 702 00 | Czechia |
| Nimbus site #XYZ | Pardubice | 530 02 | Czechia |
| Nimbus site #XYZ | Uherské Hradiště | 686 01 | Czechia |
| Nimbus site #XYZ | Zlín | 760 01 | Czechia |
| Nimbus site #XYZ | Cottbus | Brandenburg | 03042 | Germany |
| Nimbus site #XYZ | Bonn | North Rhine-Westphalia | 53127 | Germany |
| Nimbus site #XYZ | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Nimbus site #XYZ | Herne | North Rhine-Westphalia | 44649 | Germany |
| Nimbus site #XYZ | Ratingen | North Rhine-Westphalia | 40878 | Germany |
| Nimbus site #XYZ | Berlin | 12161 | Germany |
| Nimbus site #XYZ | Berlin | 14059 | Germany |
| Nimbus site #XYZ | Hamburg | 20095 | Germany |
| Nimbus site #XYZ | Hamburg | 22415 | Germany |
| Nimbus site #XYZ | Krakow | Lesser Poland Voivodeship | 30-033 | Poland |
| Nimbus site #XYZ | Lublin | Lublin Voivodeship | 20-607 | Poland |
| Nimbus site #XYZ | Elblag | Warmian-Masurian Voivodeship | 82-300 | Poland |
| Nimbus site #XYZ | Bialystok | 15-077 | Poland |
| Nimbus site #XYZ | Bydgoszcz | 85-065 | Poland |
| Nimbus site #XYZ | Krakow | 30-149 | Poland |
| Nimbus site #XYZ | Krakow | 30-363 | Poland |
| Nimbus site #XYZ | Nadarzyn | 05-830 | Poland |
| Nimbus site #XYZ | Nowa Sól | 67-100 | Poland |
| Nimbus site #XYZ | Poznan | 60-218 | Poland |
| Nimbus site #XYZ | Poznan | 61-293 | Poland |
| Nimbus site #XYZ | Poznan | 61-397 | Poland |
| Nimbus site #XYZ | Poznan | 61-731 | Poland |
| Nimbus site #XYZ | Sochaczew | 96-500 | Poland |
| Nimbus site #XYZ | Torun | 87-100 | Poland |
| Nimbus site #XYZ | Warsaw | 02-665 | Poland |
| Nimbus site #XYZ | Wroclaw | 50-244 | Poland |
| Nimbus site #XYZ | Wroclaw | 51-318 | Poland |
| FG002 | NDI-034858 Medium Dose | Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| FG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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Full Analysis Set included all randomized participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo capsules, orally, QD for 12 weeks. |
| BG001 | NDI-034858 Low Dose | Participants received NDI-034858 low dose, capsules, orally, QD for 12 weeks. |
| BG002 | NDI-034858 Medium Dose | Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| BG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Height | Mean | Standard Deviation | centimeters (cm) |
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| Weight | Mean | Standard Deviation | kilograms (kg) |
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| Body Mass Index (BMI) | BMI = weight (kg)/[height (m)^2] | Mean | Standard Deviation | kilograms per meter square (kg/m^2) |
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| 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 | Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | ACR20 is composite measure defined as improvement of 20 percent(%) from baseline in both number of tender (68) & number of swollen (66) joints & a 20% improvement in at least 3 of following 5 criteria: patient global assessment of psoriatic arthritis (PGA-PsA) [visual analog scale (VAS) where, 0=very good, no symptoms & 100=very poor, severe symptoms], physician global assessment of psoriatic arthritis (PhGA-PsA) [(VAS) where 0=no disease activity & 100=maximum disease activity], patient global assessment of psoriatic arthritis pain (PGAAP) [(VAS) where 0=no pain & 100=most severe pain], disability history questionnaire i.e., Health Assessment Questionnaire-Disability Index [HAQ-DI] (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip & activities, 0=without difficulty to 3=unable to do) & acute phase reactant like high sensitivity C-reactive protein [hsCRP]). Percentages are rounded off to the nearest decimal. | Full Analysis Set included all randomized participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | The ACR-50 is a composite measure defined as improvement of 50% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 50% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA [(VAS) where 0=no disease activity and 100=maximum disease activity], PGAAP [(VAS) where 0=no pain & 100=most severe pain], disability history questionnaire (i.e., HAQ-DI) [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do] and an acute phase reactant [i.e., erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)]. Percentages are rounded off to the nearest decimal. | Full Analysis Set included all randomized participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | The ACR-70 is a composite measure defined as improvement of 70% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 70% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA [(VAS) where 0=no disease activity and 100=maximum disease activity], PGAAP [(VAS) where 0=no pain & 100=most severe pain], disability history questionnaire (i.e., HAQ-DI) [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do] and an acute phase reactant (i.e., ESR or CRP). Percentages are rounded off to the nearest decimal. | Full Analysis Set included all randomized participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Change From Baseline in Tender Joint Count (TJC) at Week 12 | The TJC 68 is a total score of points assigned for the presence of tenderness in the 68 joints in the upper body and upper/lower extremity. The response to tenderness for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all tender joints was derived. The overall tender joint count ranged from 0 to 68, with a higher score indicating a greater degree of tenderness. A negative change from baseline indicates improvement. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | tender joints | Baseline, Week 12 |
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| Secondary | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | The SJC 66 (TJC 68 joint assessment minus hip joints, which cannot be assessed for swelling) is a total score of points assigned for presence of swelling in the 66 joints in the upper body and upper/lower extremity. The response to swelling for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all swollen joints was derived. The overall swollen joint count ranged from 0 to 66, with a higher score indicating a greater degree of swelling. A negative change from baseline indicates improvement. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | swollen joints | Baseline, Week 12 |
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| Secondary | Change From Baseline in PGA-PsA at Week 12 | Participants assessed their overall disease status based on symptoms of psoriasis and psoriatic arthritis at the time of the visit using the PGA-PsA VAS of 100 millimeters (mm) which ranges from 0 (very good, no symptoms) to 100 (very poor, severe symptoms). A negative change from Baseline indicates improvement in symptoms. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | mm | Baseline, Week 12 |
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| Secondary | Change From Baseline in PGAAP at Week 12 | Participants assessed their overall psoriatic arthritis-related pain at the time of the visit using the PGAAP VAS of 100 mm which ranges from 0 (no pain) to 100 (most severe pain). A negative change from Baseline indicates improvement in pain. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | mm | Baseline, Week 12 |
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| Secondary | Change From Baseline in PhGA-PsA at Week 12 | The participants' overall disease status was assessed, taking into account signs, symptoms, and function, of all components of joint and skin affected at the time of the visit and this overall status was rated by the investigator using the PhGA-PsA VAS of 100 mm where 0 is 'very good, asymptomatic, and no limitation of normal activities' and 100 is 'very poor, very severe symptoms which are intolerable, and inability to carry out all normal activities'. A negative change from Baseline indicates improvement in symptoms. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | mm | Baseline, Week 12 |
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| Secondary | Change From Baseline in HAQ-DI Total Score at Week 12 | The HAQ-DI consists of 20 questions referring to eight domains consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored from 0 (without any difficulty) to 3 (unable to do). The worst score within each domain will be used as the domain score (i.e., if the score for one question is 1 and 2 for the other, then the worst score for the domain is 2). The HAQ-DI total score is calculated by dividing the sum of the domain scores by the number of non-missing domains. The total score indicates the patient's self-assessed level of functional ability and higher scores indicate worse functional ability. The HAQ-DI total score ranges from 0 to 3. A higher score indicates worse function and greater disability. A negative change from Baseline indicates improved function. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 12 |
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| Secondary | Change From Baseline in Dactylitis Count (DC) at Week 12 | Tender score (0 = no tenderness, 1 = tender, 2 = tender and wince, 3 = tender and withdraw) is collected for Dactylitis Assessments on the Dactylitis Score Sheet that is used for calculation of total score. DC equals the number of tender fingers and toes (tender score >0). For participants with dactylitis status absent for all the fingers and toes, the DC is set as 0. The total score range of DC is from 0 to 60, higher scores indicate greater presence of dactylitis. A negative change from baseline indicates improvement. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with dactylitis at Baseline and with available data. | Posted | Least Squares Mean | Standard Error | dactylitis count | Baseline, Week 12 |
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| Secondary | Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | Enthesitis is assessed using LEI. The enthesitis examination by LEI evaluates the presence or absence of pain by applying local pressure on 6 anatomical sites: medial femoral condyle (left and right), lateral epicondyle (left and right), and the achilles tendon insertion (left and right). Enthesitis at each site is scored as 0 (enthesitis absent) and 1 (enthesitis present). LEI is derived as the sum of the enthesitis score over the 6 sites, divided by the number of sites with non-missing score. The total score ranges from 0 to 6, higher scores indicate greater degree of enthesitis. A negative change from baseline indicates improvement. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants who had a baseline LEI score of ≥1 and with data available for analyses. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 12 |
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| Secondary | Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | MDA is a measure to indicate a state of minimal disease activity, and is a composite score of 7 domains. A participant is considered as having achieved the MDA if the participant fulfills at least 5 of the following 7 criteria: TJC 68 ≤1; SJC 66 ≤1; Psoriasis area and severity index (PASI) score ≤1 [The total score ranges from 0 (no disease) to 72 (maximal disease)] or body surface area (BSA) ≤3%; PGAAP ≤15 [using VAS on a scale of 0 (no pain) to 100 (serious pain)]; PGA-PsA ≤20 [using VAS on a scale of 0 (very well) to 100 (very poor)]; HAQ-DI score ≤0.5; LEI score ≤1. Percentages are rounded off to the nearest decimal. | Full Analysis Set included all randomized participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | The DAPSA score is a composite score and was calculated using: TJC68, SJC66, PGA-PsA, PGAAP, and hsCRP level (milligram per deciliter [mg/dL]). DAPSA scores 0-4 = remission, 5-14 = low disease activity, 15-28 = moderate disease activity, and >28 = high disease activity. The DAPSA score has a lower bound of 0 and has no upper bound. A higher DAPSA score indicated more active disease activity. A negative change from baseline indicates improvement. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 12 |
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| Secondary | Percentage of Participants Who Achieved PASI-75 Response at Week 12 | PASI-75 is assessed in participants with psoriasis involvement for ≥ 3% of the BSA at Baseline and assesses the extent of involvement and severity of psoriasis. To calculate the PASI, the body is divided into 4 regions: the head and neck, trunk, upper limbs, and lower limbs. Each of these areas are assessed separately for the percentage of the area involved and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90% to 100% involvement). The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). For PASI-75, the improvement threshold from baseline in PASI score is 75%. A higher score indicates more severe disease. Percentages are rounded off to the nearest decimal. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with psoriasis covering ≥ 3% of the BSA at Baseline and with available data. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | PhGA-PsO responder is defined as participants 1) who had PhGA-PsO score of 0 or 1 at any given post-baseline visit; and 2) who had at least 2-point improvement from baseline. The PhGA-PsO is measured using a 0 to 4 scale with a 0 meaning clear or a 4 meaning severe. The proportion of participants achieving PhGA-PsO response at Week 12 was calculated and analyzed for participants with a score of at least 2 at baseline. Percentages are rounded off to the nearest decimal. | Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with PhGA-PSO ≥2 at Baseline. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Adverse Event(AE)=medical occurrence that does not necessarily have a causal relationship with this drug also including clinically meaningful findings in laboratory safety tests,vital signs,weight,and electrocardiogram(ECG).TEAEs=AEs occurring at time of or post study drug dosing until study end.SAE=any medical occurrence at any dose that resulted in death,was life-threatening,required inpatient hospitalization/prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was a congenital abnormality/birth defect,an important medical event.AESIs included Common Terminology Criteria for Adverse Events(CTCAE)Grade≥2 cytopenia,CTCAE Grade≥3 elevation of creatine phosphokinase(CPK)[clinically significant or not]defined as CPK>5xupper limit of normal(ULN),infections,adverse events of abnormal liver function tests,adverse events of renal dysfunction,major adverse cardiovascular events,thromboembolic events,gastrointestinal perforation,and malignancies. | Safety Analysis Set included all randomized participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug up to end of study (up to Week 16) |
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| Secondary | Plasma Concentration of NDI-034858 | Plasma concentration of NDI-034858 was measured in participants who received low, medium, or high doses of NDI-034858. | Pharmacokinetic (PK) Analysis Set included all participants in the Safety Analysis Set with at least one evaluable post-dose PK assessment. Number analyzed is the number of participants with data available for analysis at the specified time point. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Pre-dose, 1 hour post-dose on Day 1 and Week 4, 4 hours post-dose at Week 4, Pre-dose at Week 8, and anytime at Week 12 |
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|
From first dose of study drug up to end of study (up to Week 16)
All-cause Mortality: all enrolled participants. SAEs and Other AEs: Safety Analysis Set included all randomized participants who received at least one dose of 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 | Placebo | Participants received placebo capsules, orally, QD for 12 weeks. | 0 | 75 | 4 | 72 | 13 | 72 |
| EG001 | NDI-034858 Low Dose | Participants received NDI-034858 low dose, capsules, orally, QD for 12 weeks. | 0 | 76 | 4 | 71 | 19 | 71 |
| EG002 | NDI-034858 Medium Dose | Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. | 0 | 78 | 3 | 75 | 27 | 75 |
| EG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. | 0 | 76 | 2 | 72 | 35 | 72 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 26 | Systematic Assessment |
| |
| Bell's palsy | Nervous system disorders | MedDRA 26 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 26 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA 26 | Systematic Assessment |
| |
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Gastrointestinal inflammation | Gastrointestinal disorders | MedDRA 26 | Systematic Assessment |
| |
| Oesophageal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 26 | Systematic Assessment |
| |
| Psoriatic arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 26 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 26 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 26 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 26 | Systematic Assessment |
| |
| Psoriatic arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 26 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 26 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 26, 2023 | May 3, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015535 | Arthritis, Psoriatic |
| ID | Term |
|---|---|
| D025242 | Spondylarthropathies |
| D025241 | Spondylarthritis |
| D013166 | Spondylitis |
| D013122 | Spinal Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D011565 | Psoriasis |
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Non-white |
|
| Missing |
|
| Cochran-Mantel-Haenszel | =0.002 | Risk Difference (RD) | 24.1 | 2-Sided | 95 | 8.6 | 39.6 | MH risk difference was summarized along with the 2-sided 95% CI using MH stratum weights and the Sato variance estimator. | Superiority | Comparisons of ACR20 responder rates at Week 12 were made independently between each dose group and the placebo group using two-sided MH tests stratified on randomization stratification factors: prior treatment with biologics or non-traditional DMARDs and region. |
| Cochran-Mantel-Haenszel | =0.002 | Risk Difference (RD) | 24.5 | 2-Sided | 95 | 9.0 | 39.9 | MH risk difference was summarized along with the 2-sided 95% CI using MH stratum weights and the Sato variance estimator. | Superiority | Comparisons of ACR20 responder rates at Week 12 were made independently between each dose group and the placebo group using two-sided MH tests stratified on randomization stratification factors: prior treatment with biologics or non-traditional DMARDs and region. |
Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks.
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks.
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks.
|
|
|
|
|
|
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG002 |
| NDI-034858 Medium Dose |
Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG002 | NDI-034858 Medium Dose | Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
|
Participants received NDI-034858 low dose, capsules, orally, QD for 12 weeks.
| OG002 | NDI-034858 Medium Dose | Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. |
| OG003 | NDI-034858 High Dose | Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. |
|
|
| Counts |
|---|
| Participants |
|
|