Download IND_Minutes_draft_08.06.12

Minutes of IND Committee Meeting Held on
08.06.2012
Item No.1: Phase I clinical trial with P7170.
After detailed deliberation the committee recommended for giving permission to
conduct the Phase I study subject to the condition that in preclinical studies
(Rats) effective dose (in vivo) was close to NOAEL, and even HED of NOAEL is
50 mg and of effective dose is 18mg (Ratio is only 2.7), IB should clearly
highlight this fact so that Clinical investigators should be aware of possible
toxicity on dose escalation.
Item No.2: Phase II/III clinical trial with P276-00.
After detailed deliberation the committee recommended that initially firm should
complete Phase II study. Complete analysis of Phase II data should be
submitted to the IND committee for expedited review. Committee also
recommended that firm should conduct animal toxicity study with the drug for 3
months duration as per ICH-S9 guidelines prior to initiating Phase III clinical
trial. The clinical trial sites should be geographically distributed across the
country and the details of the same alongwith undertaking from the investigators
should be submitted to the office of DCG(I).
Item No. 3: Phase III clinical trial with P276-00 + Gemcitabine.
Committee recommended that firm should conduct animal toxicity study with
the drug for 3 months duration as per ICH-S9 guidelines prior to initiating Phase
III clinical trial which should be submitted to the committee for expedited review.
Item No. 4. Phase I/II clinical trials with H1N1-09 Influenza VLP.
After detailed deliberation the committee recommended for for giving
permission to conduct Phase I/II clinical trial subject to the following conditions:
1. Phase I should be conducted on male healthy subjects only.
2. Age of subjects to be enrolled in the study should be 18-65 yrs.
3. Study should be conducted at sites which are multispeciality hospitals with
the facility of emergency backup and have their own institutional ethics
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committee. Details of the sites where the clinical trial will be conducted
alongwith undertaking from investigators etc. should be submitted to the
office of DCG(I) prior to initiation of the study.
Item No. 5. Phase I/II clinical trial with Trivalent Seasonal Influenza VLP.
After detailed deliberation the committee recommended for for giving
permission to conduct Phase I/II clinical trial subject to the following conditions:
1. Phase I should be conducted on male healthy subjects only.
2. Age of subjects to be enrolled in the study should be 18-65 yrs.
3. Study should be conducted at sites which are multispeciality hospitals with
the facility of emergency backup and have their own institutional ethics
committee. Details of the sites where the clinical trial will be conducted
alongwith undertaking from investigators etc. should be submitted to the
office of DCG(I) prior to initiation of the study.
Item No.6: i.e, Argentanon –N, Argentam-N & Amniotic membrane in
treatment of burn injuries and non healing ulcers.
After detailed deliberation the committee recommended that since the proposal
is for commercial use of the products, applicant should be asked to file a formal
new drug application in Form-44 alongwith all the details including chemical &
pharmaceutical information, preclinical and clinical data of the product as per
Schedule-Y of Drugs & Cosmetics Rules to the office DCG(I) which should be
placed before the committee for further action.
Item No.7: Phase Ib clinical trial with ZYOG1.
After detailed deliberation the committee recommended for giving permission to
conduct Phase Ib clinical trial subject to condition that DSMB should be
constituted which will routinely monitor the study.
Item No.8: Phase I clinical trial with Bioplatin.
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After detailed deliberation the committee recommended that firm should submit
following clarification / information:
1. Toxicology study in dogs is required to be conducted
2. Toxicokinetics study should have been conducted along with 90 days
chronic toxicity studies.
3. Toxic effects on haematological and biochemical laboratory parameters and
ECG have not been submitted / done in acute toxicity studies.
4. Why gum acacia was used as a vehicle in toxicity studies instead of honey?
The toxicity studies should be conducted using the same vehicle which will
be used in clinical trials of the drug.
5. The method described as a purification method of platinum is actually
adopted from the classical ayurvedic method of preparing bhasmas. It is the
process of calcinations by which a substance which is otherwise bioincompatible is made bio-compatible. Hence the word purification may be
replaced by calcinations to avoid confusion.
6. The manufacturing of the drug may be done at GMP certified facility.
7. In the monograph of Bioplatin, it has been stated that for heavy metals limit
in the product is as per the Quality Control Methods of Medicinal Plant
Materials, WHO Geneva, 1998 & IP 2007. Why the medicinal plant guideline
was used when the final product is not a herbal product?
8. In vitro screening of Bioplatin on cancer cell lines might have been done in
comparison to other approved platinum based anticancer agents to identify
the specific cancer types against which the drug has maximum activity.
9. In vitro study on CYP450 inhibition and induction might have been
conducted to rule out the drug interaction potential of Bioplatin with other
drugs that are usually prescribed to cancer patients for symptomatic relief.
10. Pharmacological studies for preliminary characterization of the mechanism
of action and to ascertain the anticancer activity of the drug in appropriate
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models may be done as per S9 ICH guidelines – Nonclinical evaluation for
anticancer pharmaceuticals.
11. Absolute oral bioavailability of the drug may be provided.
12. In the “Rationale for the proposed dose of Bioplatin” for the clinical study it
has been mentioned that the dose in chronic 90 day toxicity study in rats
was 4.32 mg/kg/day while it was 1.08 mg/kg/day/test animal as mentioned in
the toxicity report. Therefore, the human equivalent dose comes out to be
1.08/6.2 = 0.174 mg/kg and in adult of weight 65kg the dose would be 65 x
0.174 = 11.31 mg
13. In safety parameters vital signs, physical and systemic examination of the
patients must be carried out at every visit for any toxic effect.
14. Full contact information comprising name, address and contact no.s of
safety physician may be mentioned in the Patient Information Sheet.
15. RECIST criteria and Eastern Cooperative Oncology Group performance
score may be included in the assessment parameters.
16. The protocol is not as per the Indian GCP guidelines. Ethical considerations,
statistical methods, study drug management, publication policy have not
been described.
17. DSMB may be constituted that may review the safety data before escalation
to the next higher dose.
Item No.9: Phase I clinical trial with ADV-1002401.
After detailed deliberation the committee recommended for giving permission to
conduct Phase I MAD study as per the amended protocol submitted by the firm.
Item No.10: Phase II clinical trials with formulations of Alphaketoglutrate,
Atropine, Fluticasone Propionate, Alginic Acid, Alendronate Sodium and
Ca-EDTA.
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After detailed deliberation the committee advised that applicant should submit
the detailed technical reply to the point no. 1 mentioned above. The reply
should be circulated to all the members of the committee which will again be
considered in the next IND committee meeting.
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