A Phase IV, Open Label, 4-period Cross-over Study to Inve... | NCT02634073

NCT02634073

Status Module

Sponsor/Collaborators Module

Name	Class
GlaxoSmithKline	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment A: Lamivudine 300 milligram(mg)	Experimental	Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) after overnight fasting. Treatment period will be separated by at least 7 day wash out period.	Drug: Lamivudine
Treatment B: Lamivudine 300 mg + Sorbitol 3.2 g (low dose)	Experimental	Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 3.2 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period.	Drug: Lamivudine Drug: Sorbitol
Treatment C: Lamivudine 300 mg + Sorbitol 10.2 g (medium dose)	Experimental	Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 10.2 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period	Drug: Lamivudine Drug: Sorbitol
Treatment D: Lamivudine 300 mg + Sorbitol 13.4 g (high dose)	Experimental	Participant will receive single dose of Lamivudine 300 mg (30 ml of 10 mg/ml Oral Solution) + oral solution of Sorbitol 13.4 g after overnight fasting. Treatment period will be separated by at least 7 day wash out period	Drug: Lamivudine Drug: Sorbitol

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lamivudine	Drug	It is a clear, colorless to pale yellow solution with the odour of fruit. It will be provided in a 240 mL bottle with the strength of 10 mg/mL Lamivudine 300 mg (30 mL of solution) will be administered orally to the participants

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24])	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. AUC was determined using the trapezoidal rule. Analysis of variance (ANOVA), considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine Pharmacokinetic (PK) parameters.	Day 1 to Day 3 in each treatment period
Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct)	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. Time of the last measurable concentration (t) was 48 hours for all participants and all treatments. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine PK parameters.	Day 1 to Day 3 in each treatment period
Lamivudine Elimination Half-life in Plasma (t1/2)	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine t1/2.	Day 1 to Day 3 in each treatment period
Plasma Lamivudine Apparent Oral Clearance (CL/F)	Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine CL/F

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE)	An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests.
A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >=50 kilogram (kg) (110 pounds [lb]) for men and >45 kg (99 lb) for women and body mass index (BMI) within the range 18.5 - 31 kg/meter square (m^2) (inclusive).
Male or Female. Females A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Exclusion Criteria:

ALT and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Participants with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Participants with a history of cholecystectomy, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.
Corrected QT (QTc) interval according to Fridericia's formula (QTcF) > 450 milli-seconds (msec).

Notes:

The QTc is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read.
The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.
For purposes of data analysis, Corrected QT interval according to Bazett's formula (QTcB), QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medications.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- Creatinine clearance (CrCL) <60 mL/minutes (min).
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 56 days.
- The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.](streamdown:incomplete-link)

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	ViiV Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Overland Park	Kansas	66211	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29150845	Derived	Adkison K, Wolstenholme A, Lou Y, Zhang Z, Eld A, Perger T, Vangerow H, Hayward K, Shaefer M, McCoig C. Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study. Clin Pharmacol Ther. 2018 Mar;103(3):402-408. doi: 10.1002/cpt.943. Epub 2017 Dec 11.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment Sequence 1: ADBC	Participants were randomized to receive a single dose of each of the four treatments where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g. All doses were administered after an overnight fast and there was >=7days washout between each period

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Treatment A: Lamivudine 300 milligram(mg)
Treatment B: Lamivudine 300 mg + Sorbitol 3.2 g (low dose)
Treatment C: Lamivudine 300 mg + Sorbitol 10.2 g (medium dose)
Treatment D: Lamivudine 300 mg + Sorbitol 13.4 g (high dose)

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	All Treatment Groups Combined	Sixteen participants were randomized to receive one of the following 4 treatment sequences : Treatment sequence 1 : ABCD; Treatment sequence 2: DABC; Trearment sequence 3: BCDA; Treatment sequence 4: CDAB; where A: Lamivudine 300 mg, B: Lamivudine 300 mg+ Sorbitol 3.2 g, C: Lamivudine 300 mg+ Sorbitol 10.2 g, D: Lamivudine 300 mg+ Sorbitol 13.4 g.

Units	Counts
Participants	BG00016

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00040.6± 12.30

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002
Male	BG00014

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

African American/African Heritage

Title	Measurements
	BG0006

White - White/Caucasian/European Heritage

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24])

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. AUC was determined using the trapezoidal rule. Analysis of variance (ANOVA), considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine Pharmacokinetic (PK) parameters.

PK Summary Population: defined as participants who had valid lamivudine PK parameter estimates from both reference and test treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

hour (h)*microgram (mcg)/milliliter (mL)

Day 1 to Day 3 in each treatment period

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG003	D: Lamivudine 300 mg + Sorbitol 13.4 g	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.

Units	Counts
Participants	OG00016 OG00116 OG00216 OG003

Title

Denominators

Categories

AUC (0-inf); n=16, 14, 16, 13

Title	Measurements
	OG00013.2± 22.3 OG00111.3± 21.2 OG0028.93± 22.1 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA				Ratio	0.855			2-Sided	90	0.799	0.914			AUC (0-inf) comparison		Superiority or Other
OG000 OG002		ANCOVA

Primary

Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. Time of the last measurable concentration (t) was 48 hours for all participants and all treatments. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine PK parameters.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Day 1 to Day 3 in each treatment period

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002

Primary

Lamivudine Elimination Half-life in Plasma (t1/2)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period. ANOVA, considering treatment and period as fixed effects and participant as random effect, was performed using Mixed Linear Models procedure to compare the plasma lamivudine t1/2.

PK Summary Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour (Hr)

Day 1 to Day 3 in each treatment period

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Primary

Plasma Lamivudine Apparent Oral Clearance (CL/F)

PK Summary Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Liter (L)/hr

Day 1 to Day 3 in each treatment period

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Primary

Time to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag)

Serial blood sample were collected at Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose in each treatment period.

Posted

Median

Full Range

Day 1 to Day 3 in each treatment period

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.

Secondary

Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE)

An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Safety Population: defined as all participants who enrolled into the study and received at least one dose of study drug.

Posted

Number

Participants

Up to 5 Weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.

Secondary

Change From Baseline in Pulse Rate

Change from Baseline for pulse rate was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

Safety Population.Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Posted

Mean

Standard Deviation

Beats/min

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Change From Baseline in Body Temperature

Change from Baseline for body temperature was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

Safety Population

Posted

Mean

Standard Deviation

Degree centigrade

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.

Secondary

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Change from Baseline for DBP and SBP was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period.

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Posted

Mean

Standard Deviation

millimeter of mercury (mmHg)

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Number of Participants With Treatment Emergent Laboratory Abnormality Grade

Division of Acquired immune deficiency syndrome (DAIDS) Table AE grades 1, 2, 3, and 4 of laboratory abnormalities were applied and grade were summarized by treatment and day and were listed by participant, treatment, day, and actual date and time. Treatment emergent grades are defined as any new toxicity grades or the worsened grades compared to Baseline grade. Treatment emergent lab abnormality Grade 1 for aspartate aminotransferase and sodium at follow-up visit are summarized.

Safety Population

Posted

Number

Participants

Up to Week 5

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002

Secondary

Change From Baseline in Erythrocytes

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for erythrocytes was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

10^12 cells/L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Change From Baseline in Hematocrit

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hematocrit was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

Fraction of 1

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Change From Baseline in Hemoglobin

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for hemoglobin was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

G/L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Change From Baseline in Mean Corpuscular Hemoglobin (MCH)

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCH was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

Picogram

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Change From Baseline in Mean Corpuscular Volume (MCV)

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for MCV was calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

Femtoliter

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Secondary

Change From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.

Secondary

Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for BUN, sodium, potassium, glucose, calcium were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

millimole (mmol)/L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002

Secondary

Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for AST, ALT and alkaline phosphatase were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

Unit (U)/L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002

Secondary

Change From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for creatinine and direct bilirubin were calculated as the post-dose visit value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/period. Change from Baseline in total bilirubine was not assessed. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

micromole (umol)/L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.

Secondary

Change From Baseline in Albumin

Blood samples were collected at Day -1, Day 3 of every treatment period and at follow-up. Change from Baseline for albumin was calculated as the post-dose Visit Value minus the value at Baseline, at Day 3 and Follow-up. Baseline value used in the analysis was the latest pre-dose values on Day 1 of each treatment/Period. Day -1 presented the Baseline absolute values; Day 3 and Follow-Up presented the changes from Baseline.

Safety Population

Posted

Mean

Standard Deviation

G//L

Baseline and up to 5 weeks

ID	Title	Description
OG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.
OG002	C: Lamivudine 300 mg + Sorbitol 10.2 g

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	A: Lamivudine 300 mg	After overnight fasting, participants received a single dose of treatment A: lamivudine 300 milligram (mg) (30 millilitre (mL) of 10 mg/mL oral solution) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	16	1	16
EG001	B: Lamivudine 300 mg + Sorbitol 3.2 g	After overnight fasting, participants received a single dose of treatment B: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 3.2 grams (g) in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	16	2	16
EG002	C: Lamivudine 300 mg + Sorbitol 10.2 g	After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	16	1	16
EG003	D: Lamivudine 300 mg + Sorbitol 13.4 g	After overnight fasting, participants received a single dose of treatment D: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 13.4 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.	16	1	16

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Gastroenteritis	Infections and infestations	MedDRA Verion 17.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0020 affected16 at risk EG0030 affected16 at risk
Vaginal infection	Infections and infestations	MedDRA Verion 17.0	Systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0020 affected16 at risk EG003
Vessel puncture site pain	General disorders	MedDRA Verion 17.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0020 affected16 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Verion 17.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0020 affected16 at risk EG003
Dizziness	Nervous system disorders	MedDRA Verion 17.0	Systematic Assessment	EG0000 affected16 at risk EG0010 affected16 at risk EG0021 affected16 at risk EG003

ID	Term
D007239	Infections
D000163	Acquired Immunodeficiency Syndrome

Ancestor Terms

ID	Term
D015658	HIV Infections
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D012897	Slow Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

ID	Term
D019259	Lamivudine
D013012	Sorbitol

Ancestor Terms

ID	Term
D016047	Zalcitabine
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D015224	Dideoxynucleosides
D013402	Sugar Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D002241	Carbohydrates

After overnight fasting, participants received a single dose of treatment C: lamivudine 300 mg (30 mL of 10 mg/mL oral solution) and an oral solution containing sorbitol 10.2 g in one of the four treatment periods according to randomisation. There was a washout period of 7 days between the doses.