BioavailabilityPhase 1NCT03905564
A Study to Investigate Differences in the Extent and Rate of Absorption of Doxylamine/Pyridoxine From 2 Different Products Under Fasting Conditions
A Phase 1 study testing doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination and Diclegis (Registered Trademark) in people with Bioavailability, run by Grünenthal GmbH.
Trial summary
The purpose of the study is to investigate any difference in the extent and rate of absorption of doxylamine between the test (investigational medicinal product [IMP]) and reference products that could impact the bioavailability of the medication when administered under fasting conditions. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Bioavailability
- What is being tested?
- doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination and Diclegis (Registered Trademark)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2019to Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participation will be voluntary and according to the guidelines proposed by the Health General Law and informed consent will be obtained according to the previously mentioned law. In addition, the study will be conducted according to the ethical principles that have their origin in the Declaration of Helsinki, the review of Brazilian laws, and Good Clinical Practice.
- Only healthy female participants aged between 18 and 55 years will be included.
- The body mass index must be between 18.0 and 27.0 kilograms per square meter according to the Quetelet index.
- Participants must be willing to use contraceptive methods (including barrier methods, non-hormonal intra-uterine device, or have a preexistent bilateral tubal ligation) during the conduct of the study and for up to 3 weeks after the last dose is administered.
- Participants must be healthy as determined by the results of a complete clinical history recorded by the clinical investigational site physicians and the results of the laboratory examinations and 12-lead electrocardiogram done by a certified clinical laboratory.
- The allowed limits of variation within normal in the screening visit will be: systolic blood pressure (sitting) less or equal to 120 mmHg, diastolic blood pressure less or equal to 80 mm Hg, heart rate between 50 and 100 beats per minute and respiratory rate between 14 and 20 breaths per minute according to the current standard operating procedure. Vital signs will be measured after 10 minutes of resting in a sitting position.
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- Laboratory and other examinations to be conducted for the inclusion of participants will be:
- Complete blood count: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte distribution width, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils.
- Blood chemistry 27 elements: glucose, urea, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, uric acid, cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein cholesterol, non-HDL cholesterol, atherogenic index, total protein, albumin, globulins, albumin/globulin ratio, total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, total alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, iron, calcium, sodium, potassium, and chloride.
- Urinalysis: Physical examination (color, appearance, density); chemical examination (pH, leukocytes, nitrite, protein, glucose, ketones, bilirubin, urobilinogen, hemoglobin); microscopic examination (leukocytes, erythrocytes, dysmorphic erythrocytes, casts, crystals, squamous epithelial cells, tubular renal cells, mucus, bacteria and yeasts).
- Hepatitis B screening (Anti-HBc = Antibody to hepatitis B core antigen, HBs-Ab = antibody to hepatitis B surface antigen, Anti-HBs = antibody to hepatitis B surface antigen) and hepatitis C antibodies.
- HIV test: Antibodies to the human immunodeficiency virus (Anti-HIV 1 and 2).
- Venereal disease research laboratory (VDRL) test.
- Urine drugs of abuse test at the screening visit and at approximately 12 hours prior to the administration of the IMP in both study periods.
- Alcohol breath test approximately 12 hours prior to the administration of the IMP in both study periods.
- Serum pregnancy test (beta-human chorionic gonadotropin) at the screening visit and urine pregnancy test (qualitative) at approximately 12 hours prior to the administration of the IMP in both study periods.
- 12-lead electrocardiogram which will be performed after resting for 10 minutes in a sitting position.
Who cannot join
- Participants with a history of the following diseases: cardiovascular, renal, hepatic, muscular, metabolic, gastrointestinal, neurologic, psychiatric, hematopoietic, respiratory, urinary, or other organic abnormalities as well as those participants who have had muscular trauma within 21 days previous to the study will also be excluded.
- Participants who require any kind of medication during the course of the study, apart from the IMP.
- Participants with a history of dyspepsia, gastritis, esophagitis, duodenal, or gastric ulcer, pyloro-duodenal obstruction, asthma, and urinary bladder obstruction.
- Participants with angle-closure glaucoma.
- Current or recent (within 14 days prior to administration of the IMP) use of monoamine oxidase inhibitors (MAOIs).
- Participants who have been exposed to enzyme or hepatic inducers or inhibitors within 30 days previous to the start of the study.
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- Participants who have taken any type of medication including vitamin supplements (with or without prescription) or herbal remedies (e.g., St John's wort) within 30 days (or 7 half-lives) previous to the start of the study.
- Participants who have been hospitalized for any reason within 6 months prior to the start of the study.
- Participants who have taken IMPs from other investigations within 90 days prior to study start.
- Participants with a history of allergy or hypersensitivity to the study medication (doxylamine/pyridoxine), any other medication, food, or substance.
- Participants who have consumed alcohol, carbonated beverages and/or or beverages that contain methylxanthines (coffee, tea, cocoa, chocolate, mate, cola, etc.), grapefruit juice, or charbroiled foods within 12 hours prior to the start of the hospitalization period as well as participants who have smoked tobacco within 12 hours prior to the study start.
- Participants who have donated or lost more than 450 milliliters of blood within 60 days prior to study start.
- Current or recent use of depressants of the central nervous system such as alcohol.
- Participants with a history of dependence/abuse of alcohol, psychoactive substances or chronic use of medications.
- Participants requiring a special diet for any reason, e.g., vegetarian.
- Participants unable to understand the nature, objectives, and possible consequences of the study.
- Evidence of the participant's uncooperativeness during the conduct of the study.
- Participants with positive test results for drugs of abuse, pregnancy and/or alcohol in breath.
- Participants currently lactating.
- Participants receiving hormonal therapy via any route of administration.
- Participants who are not registered in the Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) webpage.
- Relationship of subordination between the participants and the investigators.
- Sponsor or clinical site employees.
About this study
Official title: Single Site, Open-label, Randomized, Two Treatments, Two Periods, Two Sequences, Crossover Trial to Evaluate the Bioequivalence of Two Delayed-release Oral Formulations of a Fixed Combination of Doxylamine Succinate 10 mg/Pyridoxine Hydrochloride 10 mg (Test Product: Product of Tecnandina, S.A. TENSA; Reference Product: Diclegis (Registered Trademark) Product of Duchesnay Inc.) After a Single Administration of Two Tablets to Healthy Women Under Fasting Conditions
The purpose of the study is to investigate any difference in the extent and rate of absorption of doxylamine between the test (investigational medicinal product [IMP]) and reference products that could impact the bioavailability of the medication when administered under fasting conditions.
Read the detailed description
The objective of the study is to compare the bioavailability of doxylamine between two oral delayed-release formulations containing the fixed-dose combination of doxylamine succinate 10 milligrams (mg)/pyridoxine hydrochloride 10 mg
- A product of Tecnandina, S.A. TENSA (Test) and
- Diclegis (Registered Trademark), a product of Duchesnay Inc.(Reference) after an administration of a single dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg (i.e., 2 tablets) under fasting conditions to determine bioequivalence in terms of rate and extent of absorption.
Furthermore, the tolerability of the fixed-dose combination doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg will be evaluated in healthy women in a dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg.
- Conditions
- Bioavailability
- Being tested
- doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination, Diclegis (Registered Trademark)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combinationDrug
Delayed-release tablet containing a fixed-dose combination of doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg (product of Tecnandina, S.A. TENSA).
Diclegis (Registered Trademark)Drug
Delayed-release tablet containing a fixed-dose combination of doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg (product of Duchesnay Inc.).
| Study group | Role | What they receive |
|---|---|---|
| Doxylamine succinate/pyridoxine hydrochloride | Experimental | Oral single dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg (i.e., 2 tablets doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination) administered with 250 mL of water (at room temperature) under fasting conditions. Receives: Drug: doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination |
| Diclegis (Registered Trademark) | Active comparator | Oral single dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg (i.e., 2 tablets) administered with 250 mL of water (at room temperature) under fasting conditions. Receives: Drug: Diclegis (Registered Trademark) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration curve from the administration until the time t (AUC0-t) of doxylamine
19 plasma samples will be collected from pre-dose to 48 hours post-dose. Doxylamine plasma concentrations will be determined using a high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay.
Measured: From pre-dose to 48 hours post-dose
Maximum plasma concentration (Cmax) of doxylamine
19 plasma samples will be collected from pre-dose to 48 hours post-dose. Doxylamine plasma concentrations will be determined using a high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay.
Measured: From pre-dose to 48 hours post-dose
Secondary outcomes (2)
Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of doxylamine
19 plasma samples will be collected from pre-dose to 48 hours post-dose. Doxylamine plasma concentrations will be determined using a high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay.
Measured: From pre-dose to 48 hours post-dose
Time to maximum plasma concentration (Tmax) for doxylamine
19 plasma samples will be collected from pre-dose to 48 hours post-dose. Doxylamine plasma concentrations will be determined using a high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Tmax will be calculated based on Cmax data for doxylamine.
Measured: From pre-dose to 48 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study startJun 2019 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionJun 2020 (estimated)
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BioavailabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, single-dose with two periods, two sequences (AB, BA; A = Reference and B = Test) crossover study in healthy participants under fasting conditions. Washout period between the two study periods will be at least 20 days.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grünenthal GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Grünenthal, S.A.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03905564
- Sponsor's protocol ID
- HP8012-01
- Other IDs
- DXLPRD-06-GRU, 17-CI-09 012 084
- Status last verified
- Jul 2019
- First submitted
- 20 Feb 2019
- Last updated
- 11 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Site, Open-label, Randomized, Two Treatments, Two Periods, Two Sequences, Crossover Trial to Evaluate the Bioequivalence of Two Delayed-release Oral Formulations of a Fixed Combination of Doxylamine Succinate 10 mg/Pyridoxine Hydrochloride 10 mg (Test Product: Product of Tecnandina, S.A. TENSA; Reference Product: Diclegis (Registered Trademark) Product of Duchesnay Inc.) After a Single Administration of Two Tablets to Healthy Women Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT03905564
- Acronym / sponsor ID
- HP8012-01
- Conditions
- Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Grünenthal GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Grünenthal, S.A.
- Study start
- Jun 2019 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 5 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to investigate any difference in the extent and rate of absorption of doxylamine between the test (investigational medicinal product [IMP]) and reference products that could impact the bioavailability of the medication when administered under fasting conditions.
Detailed description
The objective of the study is to compare the bioavailability of doxylamine between two oral delayed-release formulations containing the fixed-dose combination of doxylamine succinate 10 milligrams (mg)/pyridoxine hydrochloride 10 mg
- A product of Tecnandina, S.A. TENSA (Test) and
- Diclegis (Registered Trademark), a product of Duchesnay Inc.(Reference) after an administration of a single dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg (i.e., 2 tablets) under fasting conditions to determine bioequivalence in terms of rate and extent of absorption.
Furthermore, the tolerability of the fixed-dose combination doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg will be evaluated in healthy women in a dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, single-dose with two periods, two sequences (AB, BA; A = Reference and B = Test) crossover study in healthy participants under fasting conditions. Washout period between the two study periods will be at least 20 days.
| Arm | Type | Receives |
|---|---|---|
| Doxylamine succinate/pyridoxine hydrochloride | Experimental | Drug: doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combinationOral single dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg (i.e., 2 tablets doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination) administered with 250 mL of water (at room temperature) under fasting conditions. |
| Diclegis (Registered Trademark) | Active comparator | Drug: Diclegis (Registered Trademark)Oral single dose equivalent to doxylamine succinate 20 mg and pyridoxine hydrochloride 20 mg (i.e., 2 tablets) administered with 250 mL of water (at room temperature) under fasting conditions. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Participation will be voluntary and according to the guidelines proposed by the Health General Law and informed consent will be obtained according to the previously mentioned law. In addition, the study will be conducted according to the ethical principles that have their origin in the Declaration of Helsinki, the review of Brazilian laws, and Good Clinical Practice.
- Only healthy female participants aged between 18 and 55 years will be included.
- The body mass index must be between 18.0 and 27.0 kilograms per square meter according to the Quetelet index.
- Participants must be willing to use contraceptive methods (including barrier methods, non-hormonal intra-uterine device, or have a preexistent bilateral tubal ligation) during the conduct of the study and for up to 3 weeks after the last dose is administered.
- Participants must be healthy as determined by the results of a complete clinical history recorded by the clinical investigational site physicians and the results of the laboratory examinations and 12-lead electrocardiogram done by a certified clinical laboratory.
Key exclusion criteria (23 listed)
- Participants with a history of the following diseases: cardiovascular, renal, hepatic, muscular, metabolic, gastrointestinal, neurologic, psychiatric, hematopoietic, respiratory, urinary, or other organic abnormalities as well as those participants who have had muscular trauma within 21 days previous to the study will also be excluded.
- Participants who require any kind of medication during the course of the study, apart from the IMP.
- Participants with a history of dyspepsia, gastritis, esophagitis, duodenal, or gastric ulcer, pyloro-duodenal obstruction, asthma, and urinary bladder obstruction.
- Participants with angle-closure glaucoma.
- Current or recent (within 14 days prior to administration of the IMP) use of monoamine oxidase inhibitors (MAOIs).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combinationDelayed-release tablet containing a fixed-dose combination of doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg (product of Tecnandina, S.A. TENSA). | Drug | Doxylamine succinate/pyridoxine hydrochloride |
| Diclegis (Registered Trademark)Delayed-release tablet containing a fixed-dose combination of doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg (product of Duchesnay Inc.). | Drug | Diclegis (Registered Trademark) |
Primary outcome
Area under the plasma concentration curve from the administration until the time t (AUC0-t) of doxylamine
Time frame: From pre-dose to 48 hours post-dose
19 plasma samples will be collected from pre-dose to 48 hours post-dose. Doxylamine plasma concentrations will be determined using a high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay.
Maximum plasma concentration (Cmax) of doxylamine
Time frame: From pre-dose to 48 hours post-dose
19 plasma samples will be collected from pre-dose to 48 hours post-dose. Doxylamine plasma concentrations will be determined using a high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay.
2 secondary outcomes
Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of doxylamine
Time frame: From pre-dose to 48 hours post-dose
Time to maximum plasma concentration (Tmax) for doxylamine
Time frame: From pre-dose to 48 hours post-dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Grünenthal GmbH
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg combination and Diclegis (Registered Trademark) in people with Bioavailability, run by Grünenthal GmbH.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration curve from the administration until the time t (AUC0-t) of doxylamine (time frame: From pre-dose to 48 hours post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2019.