Heartburn
Conditions
Brief summary
This study will determine whether the CT formulation of famotidine taken with and without water is bioequivalent to the FCT formulation. The primary hypothesis is that the area under the concentration-time curve (AUC) and the maximum plasma concentration (Cmax) of a single dose of famotidine 20 mg CT without water are equivalent to a single dose of famotidine 20 mg FCT with water.
Interventions
DRUGFamotidine FCT
Famotidine 20 mg oral film-coated tablet taken once daily
DRUGFamotidine CT
Famotidine 20 mg oral chewable tablet taken once daily
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Female participant is not pregnant or lactating * Female of childbearing potential must use reliable means of contraception during the course of the study * Is in good health * Is able to abstain from smoking during the 24-hour periods before and during each treatment day
Exclusion criteria
* Has any major systemic disorders * Has a history of ulcers, other Gastrointestinal (GI) disease, or GI surgery * Has or has a history of any illness or condition that might interfere with optimal participation in the study * Has a history of asthma or severe allergies to drugs or foods * Currently uses prescribed or non-prescribed drugs on a regular basis * Has a recent history of drug/alcohol abuse * Consumes more than 6 cups of coffee per day * Has unconventional or extreme dietary habits * Has donated blood or has been in a clinical trial in which they received an investigational drug during the past 30 days * Has a history of allergy or intolerance to antacids * Is known to be pregnant or is not using reliable means of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From 0 to Infinity (AUC 0-∞) Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water | 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose | AUC values were natural log-transformed and analyzed using an analysis of variance (ANOVA) model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error. |
| Peak Plasma Concentration (Cmax) of Famotidine Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water | 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose | Cmax values were natural log-transformed and analyzed using an ANOVA model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC 0-∞ Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water | 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose | AUC values were natural log-transformed and analyzed using an ANOVA model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error. |
| Cmax of Famotidine Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water | 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose | Cmax values were natural log-transformed and analyzed using an ANOVA model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error. |
Participant flow
Pre-assignment details
Participants were randomized to 1 of 6 treatment sequences of 1 of 3 treatments: (1) famotidine as a film-coated tablet (FCT) taken with water, (2) famotidine as a chewable tablet (CTw) taken with water, and (3) famotidine as a chewable tablet taken without water, over 3 study periods in a crossover design.
Participants by arm
| Arm | Count |
|---|---|
| FCT With Water / CT Without Water / CT With Water Participants received famotidine 20 mg FCT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose without water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose with 120 mL of water. | 5 |
| CT Without Water / CT With Water / FCT With Water Participants received famotidine 20 mg CT as a single dose without water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg FCT as a single dosewith 120 mL of water. | 5 |
| CT With Water / FCT With Water / CT Without Water Participants received famotidine 20 mg CT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg FCT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose without water. | 5 |
| FCT With Water / CT With Water / CT Without Water Participants received famotidine 20 mg FCT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose without water. | 5 |
| CT Without Water / FCT With Water / CT With Water Participants received famotidine 20 mg CT as a single dose without water, followed by a 5- to 7-day washout, followed by famotidine 20 mg FCT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose with 120 mL of water. | 5 |
| CT With Water / CT Without Water / FCT With Water Participants received famotidine 20 mg CT as a single dose with 120 mL of water, followed by a 5- to 7-day washout, followed by famotidine 20 mg CT as a single dose without water, followed by a 5- to 7-day washout, followed by famotidine 20 mg FCT as a single dose with 120 mL of water. | 5 |
| Total | 30 |
Baseline characteristics
| Characteristic | FCT With Water / CT Without Water / CT With Water | CT Without Water / CT With Water / FCT With Water | CT With Water / FCT With Water / CT Without Water | FCT With Water / CT With Water / CT Without Water | CT Without Water / FCT With Water / CT With Water | CT With Water / CT Without Water / FCT With Water | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 5.32 | 24.0 years STANDARD_DEVIATION 7.38 | 24.2 years STANDARD_DEVIATION 4.38 | 22.6 years STANDARD_DEVIATION 3.51 | 26.4 years STANDARD_DEVIATION 6.11 | 25.6 years STANDARD_DEVIATION 6.5 | 25.9 years STANDARD_DEVIATION 6.09 |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 1 Participants | 3 Participants | 16 Participants |
| Weight | 137.6 Pounds | 163.0 Pounds | 175.4 Pounds | 147.9 Pounds | 142.6 Pounds | 180.4 Pounds | 157.4 Pounds |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 30 | 3 / 30 | 4 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Area Under the Concentration-time Curve From 0 to Infinity (AUC 0-∞) Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water
AUC values were natural log-transformed and analyzed using an analysis of variance (ANOVA) model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error.
Time frame: 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose
Population: Participants who completed the study
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Famotidine 20 mg CT Without Water | Area Under the Concentration-time Curve From 0 to Infinity (AUC 0-∞) Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water | 398.5 ng/mL hr |
| Famotidine 20 mg FCT With Water | Area Under the Concentration-time Curve From 0 to Infinity (AUC 0-∞) Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water | 394.8 ng/mL hr |
90% CI: [0.94, 1.09]
Primary
Peak Plasma Concentration (Cmax) of Famotidine Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water
Cmax values were natural log-transformed and analyzed using an ANOVA model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error.
Time frame: 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose
Population: Participants who completed the study
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Famotidine 20 mg CT Without Water | Peak Plasma Concentration (Cmax) of Famotidine Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water | 67.2 ng/mL |
| Famotidine 20 mg FCT With Water | Peak Plasma Concentration (Cmax) of Famotidine Following Single Dose Administration of Famotidine CT Without Water and Famotidine FCT With Water | 65.1 ng/mL |
90% CI: [0.93, 1.14]
Secondary
AUC 0-∞ Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water
AUC values were natural log-transformed and analyzed using an ANOVA model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error.
Time frame: 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose
Population: Participants who completed the study
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Famotidine 20 mg CT Without Water | AUC 0-∞ Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water | 440.1 ng/mL hr |
| Famotidine 20 mg FCT With Water | AUC 0-∞ Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water | 394.8 ng/mL hr |
90% CI: [1.04, 1.2]
Secondary
Cmax of Famotidine Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water
Cmax values were natural log-transformed and analyzed using an ANOVA model. The ANOVA model contained factors for participant (random effect), period, treatment, and within-participant error.
Time frame: 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24 hours post-dose
Population: Participants who completed the study
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Famotidine 20 mg CT Without Water | Cmax of Famotidine Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water | 73.0 ng/mL |
| Famotidine 20 mg FCT With Water | Cmax of Famotidine Following Single Dose Administration of Famotidine CT With Water and Famotidine FCT With Water | 65.1 ng/mL |
90% CI: [1.02, 1.24]