Trial Outcomes & Findings for A Bioequivalence Study Comparing A Fixed Dose Combination Formulation, Rin 150 And Individual Reference Drugs In Healthy Volunteers (NCT NCT02014272)
NCT ID: NCT02014272
Last Updated: 2014-07-16
Results Overview
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) was reported for rifampicin and isoniazid.
COMPLETED
PHASE1
28 participants
0 hour (pre-dose), 0.25, 0.5, 0.75, 1, 1.33 (1 hour 20 minutes), 1.67 (1 hour 40 minutes), 2, 2.33 (2 hours 20 minutes), 2.67 (2 hours 40 minutes), 3, 3.5, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1
2014-07-16
Participant Flow
Participant milestones
| Measure |
RIN 150 First, Then Rifampicin and Isoniazid
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contained 150 milligram \[mg\] rifampicin and 75 mg isoniazid) on Day 1 in first intervention period, followed by single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in second intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
Rifampicin and Isoniazid First, Then RIN 150
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in first intervention period followed by single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in second intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
|---|---|---|
|
Intervention Period 1
STARTED
|
14
|
14
|
|
Intervention Period 1
COMPLETED
|
13
|
13
|
|
Intervention Period 1
NOT COMPLETED
|
1
|
1
|
|
Washout Period 1 (7 Days)
STARTED
|
13
|
13
|
|
Washout Period 1 (7 Days)
COMPLETED
|
13
|
13
|
|
Washout Period 1 (7 Days)
NOT COMPLETED
|
0
|
0
|
|
Intervention Period 2
STARTED
|
13
|
13
|
|
Intervention Period 2
COMPLETED
|
13
|
13
|
|
Intervention Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
RIN 150 First, Then Rifampicin and Isoniazid
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contained 150 milligram \[mg\] rifampicin and 75 mg isoniazid) on Day 1 in first intervention period, followed by single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in second intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
Rifampicin and Isoniazid First, Then RIN 150
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in first intervention period followed by single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in second intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
|---|---|---|
|
Intervention Period 1
Withdrawal by Subject
|
1
|
0
|
|
Intervention Period 1
Adverse Event
|
0
|
1
|
Baseline Characteristics
A Bioequivalence Study Comparing A Fixed Dose Combination Formulation, Rin 150 And Individual Reference Drugs In Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=28 Participants
Includes all participants randomized to receive RIN 150 first and rifampicin and isoniazid first.
|
|---|---|
|
Age, Continuous
|
31.5 years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 0.25, 0.5, 0.75, 1, 1.33 (1 hour 20 minutes), 1.67 (1 hour 40 minutes), 2, 2.33 (2 hours 20 minutes), 2.67 (2 hours 40 minutes), 3, 3.5, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) was reported for rifampicin and isoniazid.
Outcome measures
| Measure |
RIN 150
n=27 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
AUClast: Rifampicin
|
85020 (nanogram*hour) per milliliter (ng*h/mL)
Geometric Coefficient of Variation 20
|
90030 (nanogram*hour) per milliliter (ng*h/mL)
Geometric Coefficient of Variation 24
|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
AUClast: Isoniazid
|
16220 (nanogram*hour) per milliliter (ng*h/mL)
Geometric Coefficient of Variation 79
|
16120 (nanogram*hour) per milliliter (ng*h/mL)
Geometric Coefficient of Variation 77
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 0.25, 0.5, 0.75, 1, 1.33 (1 hour 20 minutes), 1.67 (1 hour 40 minutes), 2, 2.33 (2 hours 20 minutes), 2.67 (2 hours 40 minutes), 3, 3.5, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest.
Cmax was reported for rifampicin and isoniazid.
Outcome measures
| Measure |
RIN 150
n=27 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Cmax: Rifampicin
|
13670 ng/mL
Geometric Coefficient of Variation 21
|
15000 ng/mL
Geometric Coefficient of Variation 28
|
|
Maximum Observed Plasma Concentration (Cmax)
Cmax: Isoniazid
|
6080 ng/mL
Geometric Coefficient of Variation 45
|
5577 ng/mL
Geometric Coefficient of Variation 37
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.25, 0.5, 0.75, 1, 1.33 (1 hour 20 minutes), 1.67 (1 hour 40 minutes), 2, 2.33 (2 hours 20 minutes), 2.67 (2 hours 40 minutes), 3, 3.5, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. Here, n=participants in the treatment group who were evaluable for this measure for specified drug of each group with reportable AUC (0 - ∞) values, respectively.
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) was reported for rifampicin and isoniazid. It is obtained from AUC (0 - t) plus AUC (t - ∞).
Outcome measures
| Measure |
RIN 150
n=27 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞): Rifampicin (n=27, 27)
|
86670 ng*h/mL
Geometric Coefficient of Variation 21
|
91340 ng*h/mL
Geometric Coefficient of Variation 24
|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞): Isoniazid (n=27, 26)
|
16680 ng*h/mL
Geometric Coefficient of Variation 78
|
17390 ng*h/mL
Geometric Coefficient of Variation 71
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.25, 0.5, 0.75, 1, 1.33 (1 hour 20 minutes), 1.67 (1 hour 40 minutes), 2, 2.33 (2 hours 20 minutes), 2.67 (2 hours 40 minutes), 3, 3.5, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. Here, n=participants in the treatment group who were evaluable for this measure for specified drug of each group with reportable t½ values, respectively.
Plasma decay half life (t1/2) was reported for rifampicin and isoniazid.
Outcome measures
| Measure |
RIN 150
n=27 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2)
t1/2: Rifampicin (n=27, 27)
|
3.608 hour
Standard Deviation 0.89531
|
3.572 hour
Standard Deviation 0.72948
|
|
Plasma Decay Half-Life (t1/2)
t1/2: Isoniazid (n=27, 26)
|
2.776 hour
Standard Deviation 1.4110
|
3.000 hour
Standard Deviation 1.4375
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.25, 0.5, 0.75, 1, 1.33 (1 hour 20 minutes), 1.67 (1 hour 40 minutes), 2, 2.33 (2 hours 20 minutes), 2.67 (2 hours 40 minutes), 3, 3.5, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1Population: Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest.
Tmax was reported for rifampicin and isoniazid.
Outcome measures
| Measure |
RIN 150
n=27 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax: Rifampicin
|
1.67 hour
Interval 0.75 to 3.52
|
1.67 hour
Interval 0.75 to 3.52
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax: Isoniazid
|
0.500 hour
Interval 0.25 to 2.67
|
0.500 hour
Interval 0.25 to 3.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening up to Day 2 of intervention period 2Population: Safety analysis set consisted of all participants who received at least 1 dose of study medication.
Criteria for clinical significant change in vital signs: systolic blood pressure (BP) less than (\<) 90 millimeters of mercury (mmHg), diastolic BP \<50 mmHg, supine and sitting heart rate \<40 beats per minute (bpm) or greater than (\>) 120 bpm, standing and erect heart rate \<40 bpm or \>140 bpm. Maximum change from baseline in systolic BP \>=30 mmHg, maximum change from baseline in diastolic BP \>=20 mmHg. Participants who met the criteria were reported.
Outcome measures
| Measure |
RIN 150
n=27 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes in Vital Signs
|
0 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening up to Day 2 of intervention period 2Population: Safety analysis set consisted of all participants who received at least 1 dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (less than \[\<\] 0.8\*lower limit of normal\[LLN\]); leucocytes (\<0.6/ greater than \[\>\] 1.5\*limit of reference range \[LRR\]); platelets (\<0.5/\>1.75\*LRR); neutrophils, lymphocytes (\<0.8/\>1.2\*LRR); eosinophils, basophils, monocytes (\>1.2\*upper LN \[ULN\]); bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (\>3\*ULN); creatinine, urea (\>1.3\*ULN); fasting glucose (\<0.6 /\>1.5\*LRR); uric acid (\>1.2\*ULN); sodium (\<0.95/\>1.05\*LRR); potassium, calcium, chloride, bicarbonate (\<0.9/\>1.1\*LRR); albumin, total protein (\<0.8/\>1.2\*LRR); creatine kinase (\>2.0\*ULN); urine red blood cells (RBCs), urine white blood cells (WBCs) (\>=20 high-powered field). Total number of participants with any laboratory abnormalities was reported.
Outcome measures
| Measure |
RIN 150
n=26 Participants
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 Participants
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities
|
4 participants
|
2 participants
|
Adverse Events
RIN 150
Rifampicin and Isoniazid
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
RIN 150
n=27 participants at risk
Single oral dose of 4 fixed dose combination (FDC) tablets of RIN 150 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) on Day 1 in either of the 2 intervention periods.
|
Rifampicin and Isoniazid
n=27 participants at risk
Single oral dose of 4 rifampicin 150 mg capsules and 3 isoniazid 100 mg tablets on Day 1 in either of the 2 intervention periods.
|
|---|---|---|
|
Gastrointestinal disorders
Mouth ulceration
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
0.00%
0/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
General disorders
Catheter site haematoma
|
0.00%
0/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
7.4%
2/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
General disorders
Catheter site pain
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
General disorders
Fatigue
|
0.00%
0/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Contusion
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
Injury, poisoning and procedural complications
Lip injury
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Headache
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
3.7%
1/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
|
Renal and urinary disorders
Chromaturia
|
96.3%
26/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
92.6%
25/27
Safety analysis population included all participants who received at least 1 dose of study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER