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1. Dec 2021

Safety, tolerability and pharmacokinetic characterisation of DACRA KBP-042 in healthy male subjects

ABSTRACT
There is a need for antidiabetic agents successfully targeting insulin sensitivity and treating obesity control at the same time. The aim of this first-in-human study was (a) to evaluate safety and tolerability, (b) to evaluate pharmacokinetics and (c) to assess indications of receptor eng…

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Authors:

  • Henriksen K,
  • Broekhuizen K,
  • de Boon WMI,
  • Karsdal MA,
  • Bihlet AR,
  • Christiansen C,
  • Dillingh MR,
  • de Kam M,
  • Kumar R,
  • Burggraaf J,
  • Kamerling IMC,
Bone, Biomarkers
22. Oct 2021

The Efficacy and Safety of Multiple Dose Regimens of Kudzu ( Pueraria lobata) Root Extract on Bone and Cartilage Turnover and Menopausal Symptoms

ABSTRACT
Background: Menopause is associated with detrimental changes in turnover of bone and cartilage and a variety of symptoms with negative impact on the quality of life. Naturally occurring isoflavones from Radix Pueraria lobata, Kudzu root, may possess chondroprotective and symptom-relieving …

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Biomarkers
1. Oct 2021

A biomarker perspective on the acute effect of exercise with and without impact on joint tissue turnover: an exploratory randomized cross-over study

ABSTRACT
Purpose: To investigate acute changes in biochemical markers of bone and cartilage turnover in response to moderate intensity exercise with and without joint impact in healthy human subjects.

Methods: A randomized, cross-over, exploratory, clinical study was conducted. Twenty healthy su…

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Rheumatology, Osteoarthritis, Biomarkers
1. Jul 2021

Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis? - An exploratory randomized cross-over trial

ABSTRACT
Objective: To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis.

Design: We conducted a randomized, cross-over, exploratory clinical study. Twenty subjects wi…

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Rheumatology, Osteoarthritis
7. May 2021

Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study

ABSTRACT
Objective: The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safet…

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Rheumatology, Osteoarthritis
1. Apr 2021

The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial

ABSTRACT
Objective: To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin.

Methods: Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100…

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Authors:

  • Guehring H,
  • Moreau F,
  • Daelken B,
  • Ladel C,
  • Guenther O,
  • Bihlet AR,
  • Wirth W,
  • Eckstein F,
  • Hochberg M,
  • Conaghan PG,
Rheumatology, Osteoarthritis, Biomarkers, Rheumatoid Arthritis
22. Mar 2021

Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis

ABSTRACT
The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease act…

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Rheumatology, Osteoarthritis
15. Dec 2020

A novel diclofenac gel (AMZ001) applied once or twice daily in subjects with painful knee osteoarthritis: A randomized, placebo-controlled clinical trial

ABSTRACT
Purpose: Osteoarthritis Research Society International (OARSI) Expert Consensus Guidelines recommend topical non-steroidal anti-inflammatory drugs as first-line medications for osteoarthritis (OA) knee pain, but several voluminous daily applications are required to achieve efficacy. There …

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Rheumatology, Osteoarthritis, Clinical Data Quality
1. Dec 2020

Clinical and Biochemical Factors Associated With Risk of Total Joint Replacement and Radiographic Progression in Osteoarthritis: Data From Two Phase III Clinical Trials

ABSTRACT
Objectives: Clinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but …

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Rheumatology, Osteoarthritis, Clinical Data Quality
8. Oct 2019

Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.

ABSTRACT
Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug.

Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.

Design, setting, and par…

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Rheumatology, Osteoarthritis, Biomarkers
3. Sep 2019

Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis.

ABSTRACT
Background: Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between …

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Rheumatology, Osteoarthritis
26. Jun 2019

Incidence of total hip and total knee replacements from the prospective epidemiologic risk factor study: considerations for event driven clinical trial design

ABSTRACT
Background: Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used…

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Rheumatology, Osteoarthritis, Biomarkers
6. Jan 2019

Protein biomarkers associated with pain mechanisms in osteoarthritis

ABSTRACT
Background: Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are …

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Authors:

  • Thudium CS,
  • Löfvall H,
  • Karsdal MA,
  • Bay-Jensen AC,
  • Bihlet AR,
Extracellular Matrix Research, Biomarkers
29. Mar 2018

Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women

ABSTRACT
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having…

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Authors:

  • Bertelsen DM,
  • Neergaard JS,
  • Bager CL,
  • Nielsen SH,
  • Secher NH,
  • Svendsen JH,
  • Bihlet AR,
  • Andersen JR,
  • Karsdal MA,
  • Christiansen C,
  • Nielsen HB,
Rheumatology, Osteoarthritis, Clinical Data Quality
17. Jan 2018

Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis

ABSTRACT
Background: Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describin…

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Biomarkers
4. Dec 2017

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

ABSTRACT
Background: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.

Methods: One thousand COPD subjects from the ob…

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Authors:

  • Leeming DJ,
  • Byrjalsen I,
  • Sand JMB,
  • Bihlet AR,
  • Lange P,
  • Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators,
  • Thal-Singer R,
  • Miller BE,
  • Karsdal MA,
  • Vestbo J,
Clinical Data Quality
1. Aug 2017

Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study

ABSTRACT
The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are t…

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Authors:

  • Neergaard JS,
  • Dragsbæk K,
  • Kehlet SN,
  • Hansen HB,
  • Hansen G,
  • Byrjalsen I,
  • Alexandersen P,
  • Lindgren LM,
  • Bihlet AR,
  • Riis BJ,
  • Andersen JR,
  • Qvist P,
  • Karsdal MA,
  • Christiansen C,
Biomarkers, Extracellular Matrix Research
19. Jan 2017

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

ABSTRACT
Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen,…

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Authors:

  • Bihlet AR,
  • Karsdal MA,
  • Sand JM,
  • Leeming DJ,
  • Roberts M,
  • Bowler R,
  • White W,
Rheumatology, Osteoarthritis, Biomarkers
2. Dec 2016

Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future

ABSTRACT
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-m…

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Authors:

  • Karsdal MA,
  • Michaelis M,
  • Ladel C,
  • Siebuhr AS,
  • Bihlet AR,
  • Andersen JR,
  • Guehring H,
  • Christiansen C,
  • Bay-Jensen AC,
  • Kraus VB,
Biomarkers, Extracellular Matrix Research
4. Oct 2016

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study

ABSTRACT
Background: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated wit…

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Authors:

  • Sand JM,
  • Leeming DJ,
  • Byrjalsen I,
  • Bihlet AR,
  • Lange P,
  • Tal-Singer R,
  • Miller BE,
  • Karsdal MA,
  • Vestbo J,
Bone, Osteoporosis
1. Oct 2016

A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis...

ABSTRACT
Objective: This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis.

Method: A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 …

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Authors:

  • Henriksen K,
  • Byrjalsen I,
  • Andersen JR,
  • Bihlet AR,
  • Russo LA,
  • Alexandersen P,
  • Valter I,
  • Qvist P,
  • Lau E,
  • Riis BJ,
  • Christiansen C,
  • Karsdal MA,
  • SMC021 investigators,
Clinical Data Quality
1. Apr 2016

The impact of clinical trial monitoring approaches on data integrity and cost-a review of current literature

ABSTRACT
Purpose: Monitoring is a costly requirement when conducting clinical trials. New regulatory guidance encourages the industry to consider alternative monitoring methods to the traditional 100 % source data verification (SDV) approach. The purpose of this literature review is to provide an o…

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Biomarkers, Clinical Data Quality
1. Jul 2015

Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD

ABSTRACT
Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical dev…

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Authors:

  • Bihlet AR,
  • Karsdal MA,
  • Bay-Jensen AC,
  • Read S,
  • Kristensen JH,
  • Sand JM,
  • Leeming DJ,
  • Andersen JR,
  • Lange P,
  • Vestbo J,
Clinical Data Quality
15. Apr 2015

Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials

ABSTRACT
Aim: The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.

Methods: We used data from three randomized…

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Rheumatology, Osteoarthritis
3. Apr 2015

Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials

ABSTRACT
Purpose: To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint str…

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Rheumatology, Osteoarthritis
1. Apr 2015

OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA

ABSTRACT
Background: The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Ar…

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