Bioavailability/Bioequivalence study

18 evidence topics · 2 sources

Objective

Primary and secondary objectives

“This study investigates the pharmacokinetics (PK) of tiratricol.” (opens the source at this quote in a new tab)
“The primary objective was to establish bioequivalence between 350μg tiratricol oblong tablets and 350μg tiratricol round tablets.” (opens the source at this quote in a new tab)
“The secondary objectives were to estimate the effect of food by comparing both 175μg and 1050μg tiratricol oblong tablet doses in fasted versus fed states, and to assess dose-proportionality of tiratricol oblong tablets in a fasted state.” (opens the source at this quote in a new tab)

Registered primary objective

“To establish bioequivalence between 350 μg Emcitate oblong tablets and 350 μg Emcitate round tablets in a fasted state (both administered as single oral doses of 1 × 350 μg tablet dispersed in water).” (opens the source at this quote in a new tab)
“To provide further information on the safety and tolerability of Emcitate oblong tablets and Emcitate round tablets following oral administration.” (opens the source at this quote in a new tab)

Location and study date

Study site, sponsor, and enrollment dates

Characteristic	Value
Study participating centre	“Quotient Sciences Limited”
Country of recruitment	“United Kingdom”
Sponsor	“Rare Thyroid Therapeutics International AB”
Protocol serial number	“Sponsor code MCT8-2023-5”
Date of first enrolment	“06/07/2023”
Date of final enrolment	“31/08/2023”

Study design

Randomized five-period crossover design

“This novel Phase 1, randomized, five-period cross-over study was a hybrid combination of a two-period cross-over and a three-period balanced incomplete block design in healthy adult male subjects (n = 30) with a washout of ≥3 days between periods.” (opens the source at this quote in a new tab)

Eligibility criteria

Key inclusion criteria

Criterion	Registered text
Age	“Aged 18 to 55 years inclusive at the time of signing informed consent”
Sex and health status	“Healthy males”
Body mass index	“Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening”
Body weight	“Weight 50 to 100 kg at screening”

Selected exclusion criteria

“Values outside the normal reference range for any of the following safety laboratory analytes: serum TSH, T3, T4, FT4, total cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, ferritin, parathyroid hormone (PTH) or sex hormone binding globulin (SHBG,) if judged by the investigator to be clinically significant at the screening visit” (opens the source at this quote in a new tab)
“Current smokers and those who have smoked within the last 12 months” (opens the source at this quote in a new tab)

Treatment

Single-dose administration

“Single oral doses of tiratricol were administered (see table).” (opens the source at this quote in a new tab)
“All subjects received the treatments for the critical assessment of bioequivalence and 3 additional ones.” (opens the source at this quote in a new tab)

Registered treatments

Treatment	Registered description
A	“350 μg Emicate® (Tiratricol) round tablet, fasted”
B	“350 μg Emicate® (Tiratricol) oblong tablet, fasted”
C	“1050 μg Emicate® (Tiratricol) oblong tablet, fasted”
D	“1050 μg Emicate® (Tiratricol) oblong tablet, fed”
E	“175 μg Emicate® (Tiratricol) oblong tablet, fasted”
F	“175 μg Emicate® (Tiratricol) oblong tablet, fed”

Study outcomes

Rationale for using AUC and maximum serum concentration as the bioequivalence endpoints

Registered primary outcome measure

“PK parameters Cmax, AUC(0-last) and AUC(0-inf) for tiratricol in serum measured using blood samples at pre-dose and multiple timepoints up to 72 h post-dose” (opens the source at this quote in a new tab)

Other assessments

“Serum tiratricol, standard PK parameters, and safety were assessed.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Planned and enrolled participants

Population	Participants
Target sample size at registration	“45”
Total final enrolment	“30”

Description of analysis sets

Safety and pharmacokinetic analysis counts by treatment

Treatment	Safety analysis	Pharmacokinetic analysis
A: round tablet, 350 micrograms, fasted	“29”	“29”
B: oblong tablet, 350 micrograms, fasted	“29”	“28”
C: oblong tablet, 1,050 micrograms, fasted	“24”	“24”
D: oblong tablet, 1,050 micrograms, fed	“20”	“20”
E: oblong tablet, 175 micrograms, fasted	“25”	“25”
F: oblong tablet, 175 micrograms, fed	“20”	“20”

Results

Participant disposition

No evidence found.

Baseline characteristics

No evidence found.

Efficacy results

Bioequivalence of oblong and round tablets

“Bioequivalence was established between 350μg tiratricol oblong and 350μg tiratricol round tablets in terms of AUC and Cmax with a serum half-life of approximately 13h for both administrations.” (opens the source at this quote in a new tab)

Food effect

“Overall exposure (AUC) was comparable between the fasted and fed state.” (opens the source at this quote in a new tab)
“Absorption was rapid in the fasted state (median Tmax 0.5 hr) but slower in the fed state (median Tmax approximately 1.5 hr), with Cmax 67–70% lower.” (opens the source at this quote in a new tab)

Dose proportionality

“Cmax following treatment with the 175μg, 350μg, and 1050μg oblong tablet doses increased proportionally with increasing dose, whereas AUC increased in a slightly greater than proportional manner with increasing dose.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Not applicable.

Safety results

Tolerability and serious adverse events

“Tiratricol was well tolerated in all doses and fasting states, with no serious adverse events recorded.” (opens the source at this quote in a new tab)

Study limitations

Summary

This single-dose crossover study enrolled 30 healthy adult male participants aged 18 to 55 years. Its results address formulation comparability, food effects, and dose proportionality. Analysis counts ranged from 20 to 29 participants per treatment, and the congress abstract does not report participant disposition, baseline demographics, adverse-event counts, or confidence intervals for the bioequivalence comparison. The registry record states that participant-level data will not be shared. Single-dose exposure in adults provides limited information on safety during lifelong treatment in children.

Data availability

“The datasets generated and/or analysed during the current study are not expected to be made available because of their high commercial sensitivity and the negligible benefit to the public of publication of results of non-therapeutic clinical trials.” (opens the source at this quote in a new tab)