04Clinical Trials

A placebo-controlled, randomized, double-blind comparative study.

Inclusion criteria Cats with CKD that meet all the following criteria:
Cats with serum creatinine≥1.6 mg/dL, urine specific
gravity< .035, T4 0.9–3.8 µg/dL
Animals used Client-owned cats with IRIS stage 2 and 3 CKD.
Efficacy evaluation: n = 63 (RAPROS® treatment group n = 31, Placebo treatment group n = 32)
Safety evaluation: n = 74 (RAPROS® treatment group: n = 36, Placebo treatment group: n = 38)
Treatment Cats were orally administered 55µg beraprost or placebo twice daily
Treatment period 180 days
Safety criteria General condition, blood test and occurrence of adverse events
Efficacy criteria

Serum creatinine, BUN, body weight, clinical score* (appetite, activeness, dehydration), QOL evaluation by owner and overall improvement evaluation by veterinarian, etc.

* Clinical Score

Appetite
0: Increase, 1: No change,
2: Daily food intake decreased by about 1/4,
3: Daily food intake decreased by more than 1/2, with at least one day per week of no food intake,
4: No food intake for 2-3 days per week
Activity
0: Hyperactive, 1: Normal, 2: Mildly hypoactive, 3: Moderately hypoactive, 4: Severely hypoactive
Dehydration
  1. 0<5% (no abnormalities),
  2. 15% (slight decrease in skin elasticity, dry mucous membrane),
  3. 27-8% apparent decrease in skin elasticity, capillary refill time (CRT) 2-3 seconds, slight enophthalmos, limbs are cold to the touch),
  4. 310% to 12% (loss of skin elasticity, CRT 3 seconds or more, significant enophthalmos, shock, involuntary muscle spasm, skin is cold to the touch),
  5. 412-15% (obvious signs of shock, moribund)

RAPROS® inhibited increase in serum creatinine and BUN1.

Serum creatinine

BUN

Data submitted to Ministry of Agriculture,
Forestry and Fisheries of Japan

  • RAPROS®treatment group
  • Placebo treatment group

Comparison within groups (pre vs post): Repeated ANOVA (♰: P <0.01, ♰♰: P <0.001)

Comparison between groups (RAPROS® treatment group vs Placebo treatment group): Factorial ANOVA (*: P <0.05, **P <0.01)

RAPROS® improved anorexia and loss of body weight. It also improved hypoactivity1.

Changes in body weight and clinical scores

Data submitted to Ministry of Agriculture,
Forestry and Fisheries of Japan

  • RAPROS®treatment group
  • Placebo treatment group

Comparison within groups (pre vs post): Repeated ANOVA (♰: P <0.01, ♰♰: P <0.001)

Comparison between groups (RAPROS® treatment group vs Placebo treatment group): Factorial ANOVA (*: P <0.05, **P <0.01)

Appetite

Body Weight

Physical Activity

Dehydration

Data submitted to Ministry of Agriculture, Forestry and Fisheries of Japan

Safety assessment of RAPROS®

All adverse events were reviewed regardless of causal relationship with RAPROS® or placebo1.

Main adverse events

Causal relationship with treatment drug Treatment group Adverse events (severity) Number of cases
Known Placebo group Vomiting (minor) 1 case
Unknown RAPROS®group Decrease in appetite and body weight (mild) 1 case
Placebo group Stroke (mild) 1 case
Vomiting blood (mild) 1 case
Increase in hepatic enzyme level (moderate) 1 case
Pilot study on target animal safety2
Healthy cats were given up to 3 times the clinical dosage of RAPROS® for 182 days.
Clinical signs, body weight, food consumption, water consumption, urinalysis, hematology, blood biochemistry, blood coagulation, ophthalmology, electrocardiography, necropsy, and histology results were recorded. None of these parameters showed any changes attributable to RAPROS® administration. Data submitted to Ministry of Agriculture, Forestry and Fisheries of Japan

References

  1. 1) Takenaka, M., Iio, A., Sato, R., Sakamoto, T., Kurumatani, H. and (2018), A Double-blind, Placebo-controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease. J Vet Intern Med, 32: 236-248. https://doi.org/10.1111/jvim.14839
  2. 2) Pre-publishing research data of Toray Industries, Inc.