UMIN-CTR Clinical Trial

Public title

Clinical test to examine the efficacy and
safety of pemafibrate

Acronym

PEMA Trial

Scientific Title

Efficacy and safety of pemafibrate in high
risk patients with coronary artery disease

Scientific Title:Acronym

PEBE Trial

Region

Japan

Condition

Hypertriglyceridemia

Classification by specialty

Medicine in general	Cardiology	Endocrinology and Metabolism
Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To examine the efficacy and safety with pemafibrate treatment compared with those of bezafibrate

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Others

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

To examine a percent change in the fasting
serum triglyceride levels from baseline to the study endpoint after the 24-week treatment with bezafibrate or pemafibrate.

Key secondary outcomes

To examine a percent change in the fasting serum HDL-C and ApoA-1 levels from baseline
to study endpoint.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Patients were randomly assigned in a 1:1 ratio to two treatments: bezafibrate of 400 mg/day or pemafibrate of 0.2 mg/day for the first 24-week treatment period.

Interventions/Control_2

Patients were randomly assigned in a 1:1 ratio to two treatments: bezafibrate of 400 mg/day or pemafibrate of 0.2 mg/day for the first 24-week treatment period.

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

75

years-old

>=

Gender

Male and Female

Key inclusion criteria

Eligible patients were men and postmenopausal women aged 20-75 years with dyslipidemia
treated with statin and CAD who showed
fasting serum TG levels of > 150 mg/dL and HDL-C levels of < 50 mg/dL in men or < 55 mg/dL in women at entry.

Key exclusion criteria

1.patients who required additional
medication for dyslipidemia during the
study period
2.fasting serum TG levels of over than 1000 mg/dl
3.type 1 diabetes mellitus or uncontrolled type 2 DM (HbA1c level of over than 8.5%)
4.familiar hypercholesterolemia
5.chronic kidney disease showing a serum
creatinine level of over than 1.5 mg/dL
6.history or complication of gallbladder
disease, cholelithiasis, pancreatitis, and malignant tumor
7.aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation to a level more than two times the upper limit of normal (ULN) range
8.uncontrolled hypertension (systolic blood pressure BP ofover tahn 160 mmHg or diastolic BP of over than 100 mmHg)
9.hemoglobin level of less than 12g/dL in men or less than 11 g/dL in women
11.recent myocardial infarction or cerebrovascular disorder within 3 months before
the study
12.hospitalization for worsening heart failure within 3 months
13.use of ezetimibe and supplements
containing eicosapentaenoic acid, and/or
docosahexaenoic acid within 3 months
before the study.
Patients were also prohibited from using agents that affect lipid metabolism,such as
thiazolidinedione, insulin,oral
corticosteroid, or protease inhibitor.

Target sample size

60

Name of lead principal investigator

1st name	Akihiro
Middle name
Last name	Nakamura

Organization

Iwate Prefectural Central Hospital

Division name

Department of Cardiology

Zip code

020-0066

Address

1-4-1 Ueda, Morioka, Japan

TEL

0196531151

Email

akihiro-nakamura@pref.iwate.jp

Name of contact person

1st name	Akihiro
Middle name
Last name	Nakamura

Organization

Iwate Prefectural Central Hospital

Division name

Department of Cardiology

Zip code

020-0066

Address

1-4-1 Ueda, Morioka, Japan

TEL

0196531151

Homepage URL

Email

akihiro-nakamura@pref.iwate.jp

Institute

Department of Cardiology, Iwate Prefectural Centgral Hospital

Institute

Department

Personal name

Organization

Iwate Prefectural Centgral Hospital

Organization

Division

Category of Funding Organization

Local Government

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Iwate Prefectural Central Hospital

Address

1-4-1 Ueda, Morioka, Japan

Tel

0196531151

Email

akihiro-nakamura@pref.iwate.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

岩手県立中央病院　循環器内科

Date of disclosure of the study information

2022

Year

05

Month

13

Day

URL releasing protocol

https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_63659/_pdf/-char/en

Publication of results

Published

URL related to results and publications

https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_63659/_pdf/-char/en

Number of participants that the trial has enrolled

60

Results

The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (-46.1% vs. -34.7%, p<0.001; 9.2% vs. 5.7%, p=0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate.

Results date posted

2022

Year

11

Month

21

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The mean age was 63 years, and 92% (n=55)
of the patients were men. The mean body mass index was 27 kg/m2, and 77% (n=46) of the patients met the Japanese criteria for MetS. Approximately 40% (n=24) of the patients had type 2 DM and 80% (n=48) had hypertension. Nearly half of the patients (n=31, 52%) received rosuvastatin as statin therapy.

Participant flow

Of 78 patients initially screened, 60 were
enrolled and randomized with 30 patients per treatment. All 60 patients completed the study and were included in both analysis sets.

Adverse events

The incidence rates of AEs were 37% (n=22) and 43% (n=26) with bezafibrate and pemafibrate treatments, respectively. Treatment related AEs occurred in one patient in each treatment group: thickening of the gallbladder with bezafibrate treatment and hot flash with pemafibrate treatment.
In the bezafibrate treatment group, SAEs occurred in five patients, of which two were related to the treatment: worsening renal function and acute cholecystitis. Conversely, in the pemafibrate treatment group, SAEs occurred in six patients, but none were related to the treatment. There were no treatment discontinuations because of AEs or SAEs.

Outcome measures

The primary efficacy endpoint was a percent
change (%Change) in the fasting serum TG levels from baseline to the study endpoint after the 24-week treatment with bezafibrate or pemafibrate. The baseline and study endpoint were defined as measurements before and after the 24-week treatment, respectively.
The secondary efficacy endpoints were %Change in the fasting serum HDL-C and Apo A-I levels from baseline to the study endpoint.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2019

Year

10

Month

30

Day

Date of IRB

2019

Year

10

Month

30

Day

Anticipated trial start date

2020

Year

02

Month

01

Day

Last follow-up date

2021

Year

07

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2022

Year

05

Month

12

Day

Last modified on

2022

Year

11

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054422