Trial Outcomes & Findings for A Study to Compare Two Tablet Forms of Tafamidis in Healthy Participants (NCT NCT05482308)
NCT ID: NCT05482308
Last Updated: 2024-05-23
Results Overview
The AUCinf was determined by AUClast+ (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis; kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2.
Results posted on
2024-05-23
Participant Flow
This is a 2-period,fixed-sequence crossover study. A total of 12 participants were randomized and assigned to study treatments.
Participant milestones
| Measure |
Variant 12.2 mg Tafamidis Free Acid Tablet ->Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet
Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet on Day 1 of Period 1, then after a washout of at least 16 days, participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet.
|
Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet ->Variant 12.2 mg Tafamidis Free Acid Tablet
Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet on Day 1 of Period 1 ,then after a washout of at least 16 days, participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Variant 12.2 mg Tafamidis Free Acid Tablet ->Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet
Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet on Day 1 of Period 1, then after a washout of at least 16 days, participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet.
|
Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet ->Variant 12.2 mg Tafamidis Free Acid Tablet
Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet on Day 1 of Period 1 ,then after a washout of at least 16 days, participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
No longer meets eligibility criteria
|
0
|
1
|
Baseline Characteristics
A Study to Compare Two Tablet Forms of Tafamidis in Healthy Participants
Baseline characteristics by cohort
| Measure |
Variant 12.2 mg Tafamidis Free Acid Tablet->Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet
n=6 Participants
Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet on Day 1 of Period 1, then after a washout of at least 16 days, participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet.
|
Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet->Variant 12.2 mg Tafamidis Free Acid Tablet
n=6 Participants
Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet on Day 1 of Period 1 ,then after a washout of at least 16 days, participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
18-44 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Customized
45-64 yerars
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Customized
>= 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2.Population: The PK parameter population was defined as all participants who received at least 1 dose of tafamidis and who had at least 1 of the PK parameters of interest calculated.
The AUCinf was determined by AUClast+ (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis; kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Variant 12.2 mg Tafamidis Free Acid Tablet (Test)
n=11 Participants
Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet, either in Period 1 or Period 2.
|
Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet (Reference)
n=12 Participants
Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet, either in Period 1 or Period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet)
|
58630 hour(h)*ng/mL
Geometric Coefficient of Variation 21
|
57060 hour(h)*ng/mL
Geometric Coefficient of Variation 25
|
PRIMARY outcome
Timeframe: Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2.Population: The PK concentration population was defined as all participants who receive dat least 1 dose of tafamidis and who had at least 1 measurable concentration of tafamidis.
Cmax was observed directly from data.
Outcome measures
| Measure |
Variant 12.2 mg Tafamidis Free Acid Tablet (Test)
n=11 Participants
Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet, either in Period 1 or Period 2.
|
Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet (Reference)
n=12 Participants
Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet, either in Period 1 or Period 2.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet)
|
875.2 ng/mL
Geometric Coefficient of Variation 22
|
926.5 ng/mL
Geometric Coefficient of Variation 22
|
Adverse Events
Variant 12.2 mg Tafamidis Free Acid Tablet (Test))
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Commercial 12.2 mg Tafamidis Free Acid Tablet (Reference)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Variant 12.2 mg Tafamidis Free Acid Tablet (Test))
n=11 participants at risk
Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet, either in Period 1 or Period 2.
|
Commercial 12.2 mg Tafamidis Free Acid Tablet (Reference)
n=12 participants at risk
Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet, either in Period 1 or Period 2.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
1/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
0.00%
0/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
General disorders
Influenza like illness
|
9.1%
1/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
0.00%
0/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
General disorders
Vessel puncture site haematoma
|
0.00%
0/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
8.3%
1/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
9.1%
1/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
0.00%
0/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.2%
2/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
0.00%
0/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
Nervous system disorders
Headache
|
9.1%
1/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
16.7%
2/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
1/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
8.3%
1/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
8.3%
1/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
18.2%
2/11 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
0.00%
0/12 • From informed consent through and including a minimum of 28 calendar days after last administration of study drug, up to 35 days.
Both non-serious adverse events (NSAEs) and serious adverse events(SAEs) were recorded on the case report form (CRF).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place