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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study is old (1973) and not conducted to regulatory guidelines or to GCP standards.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
other: Effect on blood lipid profile
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In addition to human pharmacology, the purpose of this study was to obtain evidence of its efficiency in human volunteers and to monitor a number of serum constituents to detect any possible adverse response to compound administration.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Method

Type of population:
other: Healthy volunteers
Subjects:
All volunteers included in this trial were male, ranging in age between 19 and 59 years. The presence of any clinical condition likely to alter interpretation of the results was eliminated by medical examination during the pre-experiment period. All volunteers were asked to continue with their normal dietary habits. Subjects were split into two groups at random.
Ethical approval:
not specified
Route of exposure:
oral
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
The test compound was administered orally as two 500 mg containing gelatin capsules taken with breakfast and evening meal.

Results and discussion

Clinical signs:
No major toxicological manifestations have been detected when group mean results from a number of serum parameters are considered.

Any other information on results incl. tables

1. No major adverse toxicological manifestations have been detected when group mean results from a number of serum parameters are considered.

2. Evidence of raised serum glutamate-pyruvate transaminase (SGPT) activity has been obtained in a number of subjects during the period of test compound administration and again between 7 and 14 days of the recovery period.

3. Minor elevations in serum calcium have been observed during test and recovery periods.

4. Minor reductions in Haemoglobin were observed in some Volunteers during the period of test compound administration.

5. BRL 10901 lowered serum cholesterol by about 40 when Group 1 mean results were considered. Reduced and variable hypocholesterolaemic response was detected in Group 2 Volunteers. Poor response was obtained in subjects with hypertriglyceridaemia and high levels of VLDL.

6. In association with the hypocholesterolaemic response discrete reductions in serum phospholipids and inorganic phosphate were observed during the period when test compound was administered.

7. Results obtained after standard test meal indicate that BRL 10901 is effective in reducing the normal post-prandial elevation in serum Cholesterol, Triglycerides, Phospholipids and Inorganic phosphates.

8. Significant reductions in serum beta lipoproteins and less marked elevations in alpha lipoprotein fractions were observed in conjunction with changes in serum cholesterol and phospholipids.

Applicant's summary and conclusion

Conclusions:
No major toxicological manifestations have been detected when group mean results from a number of serum parameters are considered.
Executive summary:

1. No major adverse toxicological manifestations have been detected when group mean results from a number of serum parameters are considered.

2. Evidence of raised serum glutamate-pyruvate transaminase (SGPT) activity has been obtained in a number of subjects during the period of test compound administration and again between 7 and 14 days of the recovery period.

3. Minor elevations in serum calcium have been observed during test and recovery periods.

4. Minor reductions in Haemoglobin were observed in some Volunteers during the period of test compound administration.

5. BRL 10901 lowered serum cholesterol by about 40 when Group 1 mean results were considered. Reduced and variable hypocholesterolaemic response was detected in Group 2 Volunteers. Poor response was obtained in subjects with hypertriglyceridaemia and high levels of VLDL.

6. In association with the hypocholesterolaemic response discrete reductions in serum phospholipids and inorganic phosphate were observed during the period when test compound was administered.

7. Results obtained after standard test meal indicate that BRL 10901 is effective in reducing the normal post-prandial elevation in serum Cholesterol, Triglycerides, Phospholipids and Inorganic phosphates.

8. Significant reductions in serum beta lipoproteins and less marked elevations in alpha lipoprotein fractions were observed in conjunction with changes in serum cholesterol and phospholipids.