UMIN-CTR Clinical Trial

Public title

Minodronate for glucocorticoid induced osteoporosis versus alfacalcidol

Acronym

m-GLORIA
Minodronate for GLucocorticoid induced OsteopoRosIs versus Alfacalcidol

Scientific Title

Minodronate for glucocorticoid induced osteoporosis versus alfacalcidol

Scientific Title:Acronym

m-GLORIA
Minodronate for GLucocorticoid induced OsteopoRosIs versus Alfacalcidol

Region

Japan

Condition

Glucocorticoid-induced osteoporosis

Classification by specialty

Endocrinology and Metabolism	Clinical immunology	Orthopedics

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the clinical efficacy of minodronate combined with alfacalcidol versus alfacalcidol in glucocorticoid-induced osteoporosis

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Incidence rate of vertebral fractures(during 36 months)
Percentage change in lumbar spine bone mineral density(at month 36)

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

minodronate 50mg once 4weeks + alfacalcidol 1micrcogram once daily orally

Interventions/Control_2

alfacalcidol 1micrcogram once daily orally

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

(1)Patients who are currently taking or plan to take oral glucocorticoid medication for 3 months or longer and thus require treatment as per the 'Guidelines for the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and mineral Research (2004),' and who meet at least one of the conditions below.
1 Have any existing insufficiency fracture
2 %YAM <80
3 Oral glucocorticoid daily dose >= 5mg prednisolone equivalent
(2) Aged between 20 and 85 years (both inclusive) at consent
(3) Patients who are able to walk without assistance
(4) Provided consent to participate in the study

Key exclusion criteria

(1) BMD (L1-4 or T-Hip) T score < -3.5
(2) Have 3 or more vertebral fractures between L1 and L4.
(3) Have 1 or more SQ grade 3 vertebral fractures, or 3 or more SQ grade 2 vertebral fractures.
(4) Have received a bisphosphonate preparation for 2 weeks or longer within 6 months prior to the study treatment.
(5) Have received a bisphosphonate preparation for 2 years or longer within 3 years prior to the study treatment.
(6) Have received a parathyroid hormone preparation or anti-RANKL antibody prior to the study treatment.
(7)Have received any of the following drugs that can affect bone metabolism within 8 weeks prior to the study treatment with the
(8) Have received cathepsin K inhibitor antibody or an anti-sclerostin prior to the study treatment.
(9) Have received any other investigational product for either clinical trial or post marketing trial within four month(120days) prior to the study treatment in the present study.
(10) Pregnant females or females who plan to be pregnant
(11) Have peptic ulcers
(12) Have history of gastrectomy or broad gastrointestinal resection
(13)Have diseases that are likely to delay esophageal transit such as esophagus stenosis or achalasia
(14) Cannot keep upright or sitting positioning for 30 minutes or more which taking drug.
(15)Have history of severe drug allergy of minodronate or alfacalcidol
(16)Have corrected serum calcium >= 10.4 mg/dl or < 8.0 mg/dl on the latest laboratory result.
(17)Have corrected urinary calcium > 0.4 mg/dl GF at on the latest laboratory result.
(18) Have history of urinary calculus or currently having urinary calculus.
(19)Have severe hepatic(the latest laboratory result shows AST,ALT2.5time higher than the normal range(or more than 100IU/L)) and renal dysfunction(the latest laboratory result shows eGFR<30mL/min) and cardiovascular disease
(20)Judged inappropriate to participate the study by attending physicians

Target sample size

300

Name of lead principal investigator

1st name	(1)Toshio (2)Satoshi
Middle name
Last name	(1) Matsumoto (2)Soen

Organization

(1) University of Tokushima
(2) Nara Hospital, Kinki University Faculty of Medicine

Division name

(1) Fujii Memorial Institute of Medical Sciences (2) Department of Orthopaedic Surgery and Rheumatology

Zip code

6300293

Address

(1) 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan (2) 1248-1 Otoda-cho, Ikoma, Nara 630-0293, Japan

TEL

088-633-9116

Email

toshio.matsumoto@tokushima-u.ac.jp

Name of contact person

1st name	Nobuyoshi
Middle name
Last name	Hatanaka

Organization

Linical Co., Ltd

Division name

Contract Medical Affairs Division

Zip code

5320003

Address

1-6-1 Miyahara Yodogawa-ku, Osaka, Japan

TEL

06-6150-2478

Homepage URL

Email

m-gloria@linical.co.jp

Institute

m-GLORIA research group

Institute

Department

Personal name

Organization

Ono Pharmaceutical Co.,Ltd
Astellas Pharma Inc

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kindai University Nara Hospital

Address

1248-1, Otodacho, Ikoma City, Nara

Tel

0743-77-0880

Email

tiken-jimukyoku@med.kindai.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2013

Year

11

Month

19

Day

URL releasing protocol

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014435

Publication of results

Published

URL related to results and publications

https://doi.org/10.1007/s00774-019-01077-x

Number of participants that the trial has enrolled

164

Results

The mean change from baseline in lumbar spine and proximal femur BMD was 104.0%,99.8%,103.2%,and 97.2%,respectively. The percentage of BMD change in the lumbar spine and proximal femur was significantly greater in the M group than in the A group.There was no significant difference in new vertebral fractures between the two groups.Both TRACP-5b and P1NP showed a significant decrease at 3 months after treatment in group M,and the decrease was maintained until 24 months.

Results date posted

2021

Year

12

Month

13

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

There was no difference between the two groups, except for fewer men, for lower lumbar spine BMD at baseline, and for higher fracture risk score in the Group M .
When patient characteristics were analyzed after stratifying the prevention and treatment subgroups, no differences in patient characteristics were found between the 2 therapies(i.e., minodronate combined with alfacalcidol versus alfacalcidol alone) in the prevention subgroup. There were no
differences found between the two groups in the treatment subgroup except for a lower incidence of rheumatoid arthritis
(underlying diseases) and a higher categorical fracture risk score in Group M.

Participant flow

Patients between the ages of 20 and 85 years, who have received or will receive oral glucocorticoids for at least 3 months and who met the selection criteria for this study were included.
Patients who met the exclusion criteria were also excluded from the study.
Free written consent was obtained from all patients prior to study Informed Consent Form, using a approved by the Ethical Review Committee.

Adverse events

The incidences of all adverse events were 56.6% in the　Group M and 55.8% in the Group A. Acute phase reactions　were defined as adverse events that occurred within 3 days　of starting the drug, which were observed in one patient in　the Group M and one patient in the Group A. There were
four patients with hypercalcemia including urinary calculus:　two patients in the Group M and two patients in the GroupA.
Gastrointestinal adverse events occurred in 25 patients,of which 12 (15.8%) patients were in the Group M and 13(16.9%) patients were in the Group A.　Drug-related adverse events were observed in 25 cases　in 13 (17.1%) patients in Group M and 6 cases in 6 (7.7%) patients in Group A. Of these drug-related adverse events, the most severe was colon polyps that occurred in one patient in Group A, and more moderate were liver disorder, gastroesophageal reflux disease, and gastroenteritis, which occurred
in three patients (one each) in Group M and ureterolithiasis that occurred in one patient in Group A. Gastrointestinal
drug-related adverse events occurred in 7 (9.2%) patients in the Group M and 3 (3.9%) patients in the Group A.

Outcome measures

BMD
At each time point and at 24 months, the mean percent change from baseline in lumbar spine and proximal femur BMD was significantly greater in the M group than in the A group. The mean change from baseline in lumbar BMD was 104.0% in group M and 99.8% in group A, and in proximal femoral BMD was 103.2% in group M and 97.0% in group A .
Bone turnover markers
the M group, both serum TRACP-5b and serum P1NP decreased significantly from baseline after 3 months of treatment and remained significantly decreased at 24 months.
Vertebral fracture
During the first 24 months of treatment, new cone fractures occurred in 7 patients (9.3%) in the M group and 2 patients (2.6%) in the A group. The incidence was 11.7% in group M and 3.6% in group A. There was no significant difference between the groups.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

09

Month

13

Day

Date of IRB

2013

Year

10

Month

07

Day

Anticipated trial start date

2013

Year

12

Month

01

Day

Last follow-up date

2018

Year

04

Month

23

Day

Date of closure to data entry

2018

Year

08

Month

08

Day

Date trial data considered complete

2018

Year

08

Month

10

Day

Date analysis concluded

2019

Year

03

Month

29

Day

Other related information

Registered date

2013

Year

11

Month

19

Day

Last modified on

2021

Year

12

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014435