Trial Outcomes & Findings for Study to Evaluate Safety and Toxicity of Polyphenon E (EGCG) in HIV-1-Infected Individuals (NCT NCT01433289)
NCT ID: NCT01433289
Last Updated: 2023-05-19
Results Overview
Safety of Polyphenon E (800mg, 1200mg, 1600mg EGCG twice daily for 14 days) in HIV-1-infected subjects.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
23 participants
Primary outcome timeframe
14 days
Results posted on
2023-05-19
Participant Flow
Participant milestones
| Measure |
Polyphenon E 1600 mg/Day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
5
|
6
|
|
Overall Study
COMPLETED
|
6
|
5
|
5
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Polyphenon E 1600 mg/Day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
Overall Study
Pregnancy
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Study to Evaluate Safety and Toxicity of Polyphenon E (EGCG) in HIV-1-Infected Individuals
Baseline characteristics by cohort
| Measure |
Polyphenon E 1600 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 6 participants. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 6 participants. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 6 participants. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
n=6 Participants
No active drug (Polyphenon E) is given in the Placebo group. A total of 6 participants will be in the Placebo group. 2 participants from the Placebo group will be paired with each of the active treatment groups.
Safety data from all participants will be evaluated.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
34.65 years
STANDARD_DEVIATION 11.5290 • n=5 Participants
|
28.5166 years
STANDARD_DEVIATION 6.3857 • n=7 Participants
|
27.3666 years
STANDARD_DEVIATION 4.6161 • n=5 Participants
|
34.7666 years
STANDARD_DEVIATION 9.2310 • n=4 Participants
|
31.3249 years
STANDARD_DEVIATION 3.4079 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
6 participants
n=4 Participants
|
23 participants
n=21 Participants
|
|
CD4 count
|
380 cell count (10^6 cells/L)
n=5 Participants
|
594 cell count (10^6 cells/L)
n=7 Participants
|
432 cell count (10^6 cells/L)
n=5 Participants
|
558.5 cell count (10^6 cells/L)
n=4 Participants
|
509 cell count (10^6 cells/L)
n=21 Participants
|
PRIMARY outcome
Timeframe: 14 daysSafety of Polyphenon E (800mg, 1200mg, 1600mg EGCG twice daily for 14 days) in HIV-1-infected subjects.
Outcome measures
| Measure |
Polyphenon E 1600 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
n=6 Participants
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events
Grade 1 AE Grade 1 AE- Mild; asymptomatic or mild symptoms, intervention not indicated
|
1 Participants
|
2 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Grade 2 AE- Moderate; minimal, local or noninvasive intervention indicated
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Grade 3 AE- Severe; but not immediately life-threatening; hospitalization indicated; disabling
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Grade 4 AE- Life-threatening consequences; urgent intervention indicated.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Grade 5 AE- Death related to AE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline and 14 daysMedian change of log10 HIV-1 RNA copies/ml from baseline in subjects who have completed 14 days of treatment (800mg, 1200mg, 1600mg EGCG bid) or placebo.
Outcome measures
| Measure |
Polyphenon E 1600 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=4 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
n=4 Participants
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
Median Change of log10 HIV-1 RNA Copies/ml
|
0.01 log10 HIV RNA copies/ml
Interval -0.13 to 0.8
|
-0.07 log10 HIV RNA copies/ml
Interval -0.18 to 0.58
|
0.17 log10 HIV RNA copies/ml
Interval -0.05 to 0.2
|
0.01 log10 HIV RNA copies/ml
Interval -0.18 to 0.07
|
SECONDARY outcome
Timeframe: Baseline to 14 daysThe number of participants achieving \>0.75 or 1.0 log10 reduction in HIV-1 RNA or \<400 copies/ml with 14 days of Polyphenon E (800mg, 1200mg, or 1600mg EGCG bid) or placebo.
Outcome measures
| Measure |
Polyphenon E 1600 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
n=6 Participants
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
Number of Participants Achieving > 0.75 or 1.0 log10 Reduction in HIV-1 RNA or <400 Copies/ml
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline to 14 daysThe mean change in CD4+ T lymphocyte counts when participants have had Polyphenon E (800mg, 1200mg, 1600mg EGCG bid for 14 days).
Outcome measures
| Measure |
Polyphenon E 1600 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
n=6 Participants
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
The Mean Change in CD4+ T Lymphocyte Counts
|
11.833333 10^6 cells/L
Standard Deviation 14.282857
|
16.166667 10^6 cells/L
Standard Deviation 14.282857
|
11.800000 10^6 cells/L
Standard Deviation 13.416408
|
8.166667 10^6 cells/L
Standard Deviation 14.282857
|
SECONDARY outcome
Timeframe: Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose on Days 1 and 14Population: The number of subjects who received treatment with Polyphenon E in each arm for each pharmacokinetic outcome measure \[t1/2 (h), Cmax (ng/ml), AUC 0-12h (h\*ng/ml), CL/F (L/h). Day14:Day1 ratio reported as geometric mean (90% confidence interval).
Plasma PK parameters of EGCG after single dose and at steady state (after 14 day EGCG treatment).
Outcome measures
| Measure |
Polyphenon E 1600 mg/Day
n=6 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=5 Participants
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
No active drug (Polyphenon E) was administered
|
|---|---|---|---|---|
|
Composite of Pharmacokinetics Time Frame: Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose
t 1/2
|
1.08 Ratio
Interval 0.74 to 1.56
|
1.14 Ratio
Interval 0.9 to 1.43
|
0.9 Ratio
Interval 0.69 to 1.18
|
—
|
|
Composite of Pharmacokinetics Time Frame: Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose
Cmax
|
1.21 Ratio
Interval 0.78 to 1.9
|
1.33 Ratio
Interval 0.65 to 2.74
|
0.65 Ratio
Interval 0.45 to 0.92
|
—
|
|
Composite of Pharmacokinetics Time Frame: Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose
AUC 0-12
|
1.4 Ratio
Interval 1.08 to 1.82
|
1.28 Ratio
Interval 0.61 to 2.69
|
0.88 Ratio
Interval 0.63 to 1.22
|
—
|
|
Composite of Pharmacokinetics Time Frame: Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose
CL/F
|
0.75 Ratio
Interval 0.58 to 0.97
|
0.81 Ratio
Interval 0.4 to 1.67
|
1.21 Ratio
Interval 0.86 to 1.71
|
—
|
Adverse Events
Polyphenon E 1600 mg/Day
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Polyphenon E 2400 mg/Day
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Polyphenon E 3200 mg/Day
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Polyphenon E 1600 mg/Day
n=6 participants at risk
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Polyphenon E: There will be three dose levels, each consisting of 6 participants. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each dose level is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each dose level. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 2400 mg/Day
n=6 participants at risk
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Polyphenon E: There will be three dose levels, each consisting of 6 participants. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding dose level will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each dose level is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Polyphenon E 3200 mg/Day
n=5 participants at risk
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Polyphenon E: There will be three dose levels, each consisting of 6 participants. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding dose level will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each dose level is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
|
Placebo
n=6 participants at risk
No active drug (Polyphenon E) is given in the Placebo group. A total of 6 subjects will be in the placebo group. 2 subjects will be randomized to take placebo in each of the active treatment groups.
Safety data from all participants will be evaluated.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Mild abdominal cramps
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/5 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Gastrointestinal disorders
Loose stools
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/5 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Nervous system disorders
Mild headache
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/5 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/5 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/5 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Respiratory, thoracic and mediastinal disorders
Decreased carbon dioxide
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
16.7%
1/6 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/5 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Gastrointestinal disorders
Elevated lipase
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Gastrointestinal disorders
Elevated SGPT
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Endocrine disorders
Decreased serum calcium
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Gastrointestinal disorders
Elevated SGOT
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Metabolism and nutrition disorders
Elevated serum protein
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
|
Metabolism and nutrition disorders
Decreased serum Magnesium level
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
20.0%
1/5 • Number of events 1 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
0.00%
0/6 • Adverse event data were collected for the 14-day study period and 7- day follow up period for a total of 21 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place