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An open-label study of FPF1011 in patients with cerebrotendinous xanthomatosis (phase 3)

An open-label study of FPF1011 in patients with cerebrotendinous xanthomatosis (phase 3)

15

The patient diagnosed with cerebrotendinous xanthomatosis Subjects administered FPF1011 were 10 males (66.7%) and 5 females (33.3%), and their age (mean +- SD) at the time of consent was 47.5 +- 8.2 years.

All 15 subjects met the inclusion criteria, were enrolled, and administered FPF1011. Two subjects discontinued the study.

Adverse events were observed in 11 of 15 subjects (73.3%). Adverse events observed in two or more subjects were pyrexia (4 subjects: 26.7%), contusion (3 subjects: 20.0%), nasopharyngitis (2 subjects: 13.3%), and hepatic function abnormal (2 subjects: 13.3%). Side effects were observed in 3 subjects (20.0%). They were hepatic function abnormal (2 subjects: 13.3%) and flatulence (1 subject 6.7%), both of which are already known side effects of CDCA. Serious adverse events observed were cholelithiasis (1 case: 6.7%, moderate) and pyrexia (1 case: 6.7%, mild). No serious side effects were observed.

Serum cholestanol concentrations In 15 subjects, serum cholestanol (mean +- SD) was 22.25 +- 12.66 mcg/mL at the time of diagnosis, 8.66 +- 7.70 mcg/mL at baseline, and 6.39 +- 5.32 mcg/mL at the final evaluation. Compared to the time of diagnosis, serum cholestanol was lower at baseline, and remained low throughout the FPF1011 administration period.

MMSE-J In 15 subjects, MMSE-J score (mean +- SD) was 26.5 +- 4.1 at baseline and 25.3 +- 4.4 at the final evaluation, remained as similar as the score at baseline throughout the FPF1011 administration period. Rankin Scale In 14 subjects excluding one subject whose data at baseline was missing, Rankin Scale score showed improvement compared to baseline in two subjects, and temporarily worsened before recovering to the same score at baseline in one subject. The remaining subjects remained unchanged throughout the FPF1011 administration period. MRI (brain and spinal cord) In 14 subjects excluding one subject whose data at the time of discontinued was missing, MRI (brain and spinal cord) evaluations after FPF1011 administration remained unchanged throughout the FPF1011 administration period, with no deterioration observed compared to baseline. Bone Mineral Density (DXA) In 15 subjects, Bone mineral density (DXA) measurements were as follows: BMD (lumbar spine) was 0.8435 +- 0.1308 g/cm2 at baseline (15 subjects) and 0.8676 +- 0.1380 g/cm2 at the final evaluation (14 subjects), BMD (femoral neck) was 0.6694 +- 0.1568 g/cm2 at baseline (15 subjects) and 0.6711 +- 0.1510 g/cm2 at the final evaluation (14 subjects). These measurements remained similar throughout the FPF1011 administration period to those measured at baseline, and no subjects experienced new onset or worsening osteoporosis. CTX-related diseases or symptoms In 15 subjects, there was no new onset or disappearance of CTX-related diseases or symptoms compared to baseline, except for one subject whose chronic diarrhea improved and one subject whose cerebellar ataxia worsened. The severity of CTX-related diseases or symptoms also remained unchanged.

Long-term administration of FPF1011 was confirmed to reduce serum cholestanol levels, a substance that causes various organ damage in adult CTX patients. Furthermore, no significant safety concerns were observed at doses up to 1000 mg/day.

No

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Fujimoto Pharmaceutical Corporation

1-3-40 Nishi-Otsuka, Matsubara, Osaka

kaihatsu8@fujimoto-pharm.jp

Fujimoto Pharmaceutical Corporation

1-3-40 Nishi-Otsuka, Matsubara, Osaka

+81-120-920-386

kaihatsu8@fujimoto-pharm.jp

completed

Aug. 03, 2020

Interventional

Open-labeled, multicenter study

treatment purpose

3

Main inclusion criteria.
1) The patient diagnosed with cerebrotendinous xanthomatosis.
2) Written informed consent.
3) In case of female patient of childbearing potential, the result of the pregnancy test (urine) conducted prior to registration must be negative, and she must consent to use suitable contraception not to get pregnant.
4) Outpatient.

Main exclusion criteria.
1) Patient who possibly changes the dosage and administration of restricted concomitant drugs or the usage of the restricted combination therapy.
2) Patient with the serious complications in circulation, respiratory, blood, liver, kidney, digestive system, and so on.
3) Patient with allergy to commercial CDCA formulations.
4) Breastfeeding woman.
5) Patient who has received any other investigational product or post-marketing clinical trial drug within 12 weeks prior to giving informed consent.

Both

Cerebrotendinous xanthomatosis

investigational material(s)
Generic name etc : FPF1011
INN of investigational material : Chenodeoxycholic acid
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : Dose of chenodeoxycholic acid is 750 mg/day for patients aged 18 or older, and 15 mg/kg/day under ages 18, administered orally in three divided doses a day.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
Serum cholestanol concentrations

efficacy
safety
1. Safety evaluations
a) Adverse event
b) Laboratory tests (blood, urine)
c) Vital signs [body temperature,
systolic blood pressure, diastolic blood pressure, and pulse rate]
d) Body weight
e) 12-Lead electrocardiogram at rest

2. Efficacy evaluations
a) MMSE-J
b) Rankin Scale
c) MRI (brain, spinal cord)
d) Bone density (DXA)
e) The diseases or symptoms related to cerebrotendinous xanthomatosis

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Mar. 13, 2020